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Neotame: Discovery, properties, utility

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Abstract

Neotame (NTM) is a new nonnutritive sweetener. NTM is a derivative of aspartame (APM). NTM has a clean sweet taste and a good flavour profile. It is a high-potency sweetener; it is 6000–10 000 times sweeter than sucrose, and 30–60 times sweeter than APM. NTM is a noncaloric, noncariogenic sweetener. NTM has an extensive shelf life in dry conditions. In aqueous food systems, it presents the same functionalities as APM in acidic medium, but it is significantly more stable in neutral medium. Consequently, NTM should be a useful sweetener in baked goods. NTM is compatible with reducing sugars and aldehyde-based flavouring agents. It has flavour-enhancing properties. Its relative cost is expected to be lower than sucrose or APM at sweetness equivalence. A petition was filed in the USA in December 1998 for its approval as a general use sweetener; other regulatory activities are underway in several countries.

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... Neotame is approximately 7000-13,000 times sweeter than sucrose and 30-60 times sweeter than aspartame (which is 200-300 times sweeter than sucrose) (FDA, 2002). As a close derivative of aspartame, it has the intrinsic qualities of aspartame: clean sugar-like taste, with no undesirable metallic or bitter taste, but it should be used at lower level (Nofre & Tinti, 2000). Of all sweeteners, aspartame is the most heat labile and its degradation is minimal under the pH range 4.0-5.0 ...
... Neotame has approximately the same stability as aspartame in the acidic pH range (pH 3-5.5), whereas at neutral pH, neotame is significantly more stable than aspartame. The optimal pH for neotame stability is 4.5 (Nofre & Tinti, 2000). The dimethyl butyl (DMB) substituent provides neotame with unique properties, such as remarkably amplified sweetness potency, flavour enhancing properties and stabilization during baking or pasteurization processes. ...
... Our results for pasteurized flavoured milk containing neotame were in accordance with the results of Nofre and Tinti (2000) who reported that 98.6% neotame remained after heating at 80°C/30 min (pH 3). Neotame can withstand pasteurization and high temperature, short-time processing treatments and 99% of the neotame was present after ultra high temperature processing (Neotame http://www.neotame.com/, ...
... Neotame is a non-calorie sweetener and has a sweetness factor approximately 7,000 to 13,000 times greater than sucrose and approximately 30e60 times greater than aspartame (EFSA, 2007). As a derivative of aspartame it has inherent qualities of aspartame i.e. clean sugar-like taste, with no undesirable metallic or bitter taste, but used at lower level (Nofre & Tinti, 2000). Moreover, it has additional feature over aspartame, as higher stability in the neutral pH range which allows its application in high heat processed products e.g. in baked products (Nofre & Tinti, 2000). ...
... As a derivative of aspartame it has inherent qualities of aspartame i.e. clean sugar-like taste, with no undesirable metallic or bitter taste, but used at lower level (Nofre & Tinti, 2000). Moreover, it has additional feature over aspartame, as higher stability in the neutral pH range which allows its application in high heat processed products e.g. in baked products (Nofre & Tinti, 2000). It is composed of two amino acids L-aspartic acid and L-phenylalanine and an additional 3, 3-dimethylbutyl group. ...
... The observations were in accordance with the results obtained by Nofre and Tinti (2000). Kumari, Choudhary, Arora, and Sharma (2016) reported 8% and 50% loss of neotame during pasteurization (90 C/20 min) and sterilization (121 C/15 min), respectively in pasteurized and in-bottle sterilized flavoured milk. ...
Article
A solid phase extraction method using C18 cartridge was standardized for the isolation of neotame from cake and ice cream. High performance liquid chromatography (HPLC) method was developed and validated for estimation of neotame in cake and ice cream. The developed HPLC method was simple, precise, accurate, reproducible and sensitive. Mobile phase consisted of 0.09 % TFA, acetonitrile:water (60:40) and the flow rate was maintained at 0.6 ml/min. HPLC separation of neotame was carried out on a reverse phase C18 column with photo diode array detector at 210 nm. The recovery of neotame from cake and ice cream by the developed method ranged from 96.08 to 98.62 %. At baking temperature (180 °C/20 min) 87.29 % of the neotame remained intact, however the amount of neotame decreased significantly from 87.20 to 62.40 % during storage (20 days at 25 °C). Pasteurization (68 °C/30 min) resulted in no loss of neotame in ice cream mix; however the amount of neotame decreased significantly from 99.42 to 89.93 % during storage (90 days at -18 °C). The developed HPLC method can be successfully used for the routine determination of neotame in cake and ice cream formulations.
... Neotame is a high potency sweetener, having sweetness factor approximately 30-60 times greater than APM (EFSA, 2007). As a close derivative of APM, it possesses the intrinsic qualities of APM: clean sugar-like taste, with no undesirable metallic or bitter taste, but used at lower level (Nofre and Tinti 2000). ...
... Like APM, NTM is relatively stable at pH levels from 3.0 to 5.5. The optimal pH for APM and NTM stability is 4.2 and 4.5, respectively (Nofre and Tinti 2000); and these sweeteners can also withstand high-temperature short-time and ultra-high-temperature conditions (Nofre and Tinti 2000;Gloria 2003). However, APM is most vulnerable when heated for an extended period of time in a high moisture system at pH > 6.0 (Wetzel and Bell 1998). ...
... Like APM, NTM is relatively stable at pH levels from 3.0 to 5.5. The optimal pH for APM and NTM stability is 4.2 and 4.5, respectively (Nofre and Tinti 2000); and these sweeteners can also withstand high-temperature short-time and ultra-high-temperature conditions (Nofre and Tinti 2000;Gloria 2003). However, APM is most vulnerable when heated for an extended period of time in a high moisture system at pH > 6.0 (Wetzel and Bell 1998). ...
Article
Full-text available
The comparative stability of aspartame and neotame was monitored in yoghurt during its processing, fermentation and storage. A solid-phase extraction method was suggest changing it to developed for the isolation of aspartame and neotame. Pasteurisation (85 °C/30 min) resulted in approximately 47% and 3% loss of aspartame and neotame, respectively. During fermentation, 3% loss of aspartame was observed, but no loss of neotame. There was no significant effects on the stability of either aspartame or neotame during storage (4–7 °C/15 days). The results indicated that neotame was more stable than aspartame under both pasteurisation and fermentation conditions; however, during storage, both sweeteners exhibited excellent stability.
... Increasing weight gain, and concerns about obesity, diabetes and cardiovascular disease, have influenced the use of artificial sweeteners in place of common sugar. Until the 1980s there were only 3 types of artificial sweeteners available: saccharin, cyclamate and aspartame, known as the first-generation sweeteners [9]. ...
... When used in very high concentrations, the sweetener has a bitter taste, so it has been associated with other sweeteners since 1950, when cyclamate was discovered [9]. ...
... With the patent for aspartame broken in 1992, and the great competition with similar products, the company developed Neotame, a derivative of aspartame, with the addition of a group 3, 3-dimethylbutyl to the free amine group of aspartic acid, which potentiates the sweetening power of the new molecule, which sweetens about 6000 to 10,000 times more than sucrose, becoming the sweetener with the highest potency ever developed. It has a good safety profile and is stable at high or low temperatures [9]. Studies show changes in body composition with the use of Neotame, such as long-term weight loss and increased consumption of unsweetened foods. ...
... Neotame is exceptionally sweet at around 8000 times sweeter than sucrose (Nofre & Tinti, 2000;Prakash et al., 2002;Nikoleli & Nikolelis, 2012). Its sweetness potency varies according to the kinds of foods and blend composition. ...
... In powder form, neotame is stable for over five years, especially at mild temperatures; its stability in solution is pH and temperature dependent with optimum stability at about pH 4.5 (Arianfar et al., 2017). Similar to aspartame, it supports heat treatment for short periods of time (Nofre & Tinti, 2000;Prakash et al., 2002;Nikoleli & Nikolelis, 2012;O'Donnell & Kearsley, 1998). ...
... In the aquatic environment the major decomposition pathway of neotame is the hydrolysis of the methyl ester group into n-[n-(3, 3dimethylbutyl)-L-α aspartyl]-L-phenylalanine and methanol, in both the acidic and the neutral pH ranges. However, this process is relatively slow (Nofre & Tinti, 2000). Often where high levels of the sweetener are detected in surface waters this is related to a direct discharge of untreated waste water nearby . ...
... As a result of this research, a noval sweetener with all the desirable characters neotame was produced. Neotame got approval fromFood and Drug Administration (FDA or USFDA) in the year 2002 (Nofre, 2000). ...
... Neotame is synthesized when tert-butyl group added to amine part of aspartic acid. Neotame is about 60 percent more sweeter than aspartame (Nofre, 2000). Neotame is quickly digested by esterase present in the body, this esterase hydrolysis the methyl ester group during metabolism. ...
... The de-esterified neotame is eliminated from human body through urine and fecal matter within 72 hours of intake. Neotame is safe sweetener for those who suffer from phenylketonuria (Nofre, 2000). ...
Article
Full-text available
Sugar gained a bitter name regards to health. Consumption of more sugars involves risk of more calories which leads to diseases like obesity, diabetes and cardiovascular problems in human body. These days food which is sugar free acquired much more reputation because of their low or no calorie content. So as a result many food industries use different low calorie artificial sweeteners instead of sugars. Food and Drug Administration (FDA or USFDA) accepted the use of six sugar substitutes (aspartame, saccharine, sucralose, neotame, acesulfame-k and stevia) safe human consumption. Advantame and extract from swingle fruit have recently discovered and added to the list of nonnutritive sweeteners. These artificial sweeteners or sugar substitutes are extensively applied in the fields of processed foods, dairy and therapeutic industries. The main aim of this review is to discuss the different types of artificial sweeteners, their history, synthesis, metabolism, uses, toxicity, therapeutic use, nontherapeutic use, health benefits and toxic effects.
... -Neotame (Fig. 1f) was developed by Monsanto. The discovery of neotame is due to the academic work of Nofre and Tinti [34]. Neotame is allowed in Australia since August 2001, and it was authorized in the United States by the FDA in 2002 [35]. ...
... Neotame should show electrostatic effects similar to aspartame, but in addition it has a hydrophobic part which may act as a cosurfactant (see Fig. 1f). Indeed, the surface tension values reported in the literature are 65 mN/m at 4 Á 10 À5 mol/l neotame concentration in water and 35 mN/m at 10 À2 mol/l, indicating that neotame can be considered as a true surfactant [34]. This together with the solubility limit of neotame in pure water (0.03 mol kg À1 at 20°C [48]) causes a more complex behavior of the corresponding T a curve in the microemulsion. ...
Article
The present paper shows the effects of added sugars and sweeteners on the clearing temperature of a highly water dilutable fatty acid salt microemulsion used as a model of a beverage concentrate. There is a twofold interest in this work. The first one is practical and relates to the fact that many fatty acid salt surfactants can be used in food without major regulatory restrictions. As is shown here, they allow making highly stable microemulsions even at neutral and acidic pH. The second one is more of scientific interest. The model system can be used to study the effect of sugars and sweeteners on the formulation stability depending on their charges, amphiphilic properties, and localization in the microemulsion interfacial film. An important practical result is the discovery of the possibility to formulate highly dilutable microemulsions at neutral or slightly acid pH with a good taste in presence of sucralose. Further, a significant decrease of the pKA of the fatty acid is observed in presence of stevia, thus allowing transparent, fairly stable systems at neutral pH. Copyright © 2015 Elsevier Inc. All rights reserved.
... It has similar physical properties as aspartame in terms of sweetness and comparable with sucrose without a metallic or bitter after taste at high concentrations. Neotame has benefits over aspartame with pH stability at neutral medium which enables its use in baking, no risk associated with the phenylketonuria individuals and being a cost effective [1][2][3] . It is significant to record that the neotame may be 13000 times sweeter that sucrose and exhibits temporal flavor profile in water, which is similar to that of aspartame, however the taste release response time is slower than aspartame 3 . ...
... Neotame in the powder form has been highly stable at mild temperature for years and it is pH and temperature dependent 1 . There are no reports available in the literature, stating that neotame is toxic to humans and other mammals, however excess usage of aspartame may cause different health issues such as memory loss, migraine and headache 4 . ...
Article
Full-text available
The metal complexes can demonstrate various interesting biological activities in the human body. However, the role of certain metal ions for specific cell activities is still subject to debate. This study is aimed at comparing the thermochemical properties of neotame (artificial sweetener) and α, β-fructose in gas phase and water medium. The interaction of α and β-fructose, neotame with monovalent and divalent metal ions was studied and comprehended by density functional theory (DFT) using B3LYP functional, 6–311 + G (d, p) and D3 basis set. Metal ion affinities (MIA) values depicted that ionic radius of metal ions played an important role in the interaction of α, β-fructose and neotame. The ∆G parameter was calculated to predict and understand the interaction of metal ions with α and β-fructose, neotame. The results suggested that the presence of hydroxyl groups and oxygen atoms in sugar molecules acted as preferred sites for the binding and interaction of mono and divalent ions. For the first time computational study has been introduced in the present study to review the progress in the application of metal binding with sugar molecules especially with neotame. Moreover, voltammetric behaviour of neotame-Zn2+ was studied using cyclic and differential pulse voltammetry. The obtained results suggest that the peak at −1.13 V is due to the reduction of Zn2+ in 0.1 M phosphate buffer medium at pH 5.5. Whereas, addition of 6-fold higher concentration of neotame to the ZnCl2.2H2O resulted in a new irreversible cathodic peak at −0.83, due to the reduction of neotame-Zn2+ complex. The Fourier transform infrared spectroscopy (FTIR) results indicates that the β-amino group (-NH) and carboxyl carbonyl (-C = O) groups of neotame is participating in the chelation process, which is further supported by DFT studies. The findings of this study identify the efficient chelation factors as major contributors into metal ion affinities, with promising possibilities to determine important biological processes in cell wall and glucose transmembrane transport.
... designed by the French scientists Claude Nofre and Jean-Marie Tinti in 1994 (1,2). Its molecular formula is C 20 H 30 N 2 O 5 , and its molecular weight is 378.47 grams/mole (2). ...
... designed by the French scientists Claude Nofre and Jean-Marie Tinti in 1994 (1,2). Its molecular formula is C 20 H 30 N 2 O 5 , and its molecular weight is 378.47 grams/mole (2). The chemical structure is given in Figure 1. ...
Chapter
Neotame is a high potency sweetener with a molecular formula of C 20H30N2O5. It is over 11,000 times sweeter by weight than sucrose at a sweetness equivalent to 5% sucrose (in water). Neotame reaches a maximum sweetness intensity equivalent to 15.1% sucrose. The temporal properties of neotame, like all other high potency sweeteners, differ somewhat from sucrose. The time of onset of sweetness of neotame is later than sucrose and it lingers longer. Cross-adaptation studies support ligand- receptor binding studies that indicate neotame along with aspartame and sucralose preferentially interact with the T1R2 subunit of the sweetener receptor. Neotame can substitute for 20-30% of the sweetness of soft drinks with no perceived difference in taste.
... Adding sweeteners to the diet may be an effective means to improve palatability and increase the feed intake of weaned piglets ( Jacela et al., 2010), since piglets like the sweet taste ( Glaser et al., 2000). Neotame is a non-nutritive artificial sweetener (N-[N-(3,3-dimethylbutyl)-l-aspartyl]-l-phenylalanine 1-methyl ester), which has a clear sweet taste like sucrose without bitter or metallic taste ( Nofre and Tinti, 2000). However, the sweetness of neotame is approximately 7,000-13,000 times greater than sucrose and 30-60 times greater than aspartame ( Aguilar et al., 2007). ...
... Studies on various species, such as mice, rats, dogs, rabbits and humans have shown that neotame is not carcinogenic, teratogenic or mutagenic and does not produce any reproductive or developmental toxicity ( Aguilar et al., 2007). Neotame has been widely used as a sweetener and flavor enhancer in the food industry ( Nofre and Tinti, 2000). Because of its clear taste and low relative cost, neotame could be an ideal feed additive for weaned pigs. ...
Article
Three experiments were conducted to evaluate the effects of a sweetener, neotame (N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester) on diet preference, performance and hematological and biochemical parameters of weaned piglets. In experiment 1, 48 weaned piglets (Duroc × Landrace × Large White), with an initial body weight (BW) of 9.05 ± 0.04 kg, were used in a diet preference study. Pigs were assigned to 8 pens with 6 pigs per pen. Each pen was equipped with two feeders, containing a maize-soybean meal based diet or a similar diet supplemented with 30 mg/kg neotame. The experiment lasted for 15 days, including a 5-d adaptation period and a 10-d experiment period. The diet supplemented with 30 mg/kg neotame was preferred (P < 0.05) by the pigs during d 7, d 10 and the entire experimental period (d 1–10). In experiment 2, 216 weaned piglets, with an initial BW of 7.35 ± 0.06 kg, blocked by gender and BW, were allocated to 1 of 6 treatments with 6 pens per treatment and 6 pigs per pen. Weaned piglets were fed the basal diet or similar diets supplemented with 10, 20, 30, 40 or 50 mg/kg neotame. The experiment lasted for 35 days. Average daily feed intake (ADFI) was improved linearly (P < 0.05) with increasing dietary neotame level during phase I (d 1–22) and the entire experimental period (d 1–35). A quadratic (P < 0.05) effect of neotame was observed on average daily gain (ADG) and ADFI during phase I (d 1–22), phase II (d 23–35) and the entire experimental period (d 1–35). The optimal concentrations of dietary neotame to maximize ADG and ADFI during entire experimental period using a fitted quadratic plot model were 21.7 and 20.7 mg/kg, respectively. Experiment 3 was conducted with 108 weaned piglets averaging an initial BW of 7.34 ± 0.08 kg to evaluate the effects of neotame on hematological and biochemical parameters of weaned piglets. Pigs were divided into 3 treatments with 6 pens per treatment and 6 pigs per pen, and fed the basal diet or similar diets supplemented with 50 or 500 mg/kg neotame. There was no difference (P > 0.05) in blood parameters, organ index and morphology among the three treatments. In conclusion, the optimal concentrations of dietary neotame for maximum ADFI and ADG was ranged from 18.0 to 20.4 mg/kg during phase I (d 1–22), 22.0 to 22.9 mg/kg during phase II (d 23–35) and 20.7 to 21.7 mg/kg during entire experimental period (d 1–35), and no adverse effects on indicators of health were observed in pigs offered diets with neotame levels up to 500 mg/kg.
... Its chemical formula is C 20 H 24 N 2 O 5 and it has a molar mass of 378.46 g/mol (Boone, 2009). The solubility in water of neotame is 12.6 g/l at 25°C (Nofre and Tinti, 2000). The solubility of neotame in water, ethyl acetate and ethanol at a range of temperatures illustrates how neotame behaves in various food matrices. ...
... In in solution, it shows highest stability at pH 4.5. At low pH, neotame a dipeptide methyl ester, hydrolyzes to the dipeptide carboxylic acid, the nonsweet major metabolite of neotame in humans (BFNE, 2010;Nofre and Tinti, 2000). ...
Article
Full-text available
Now a days sugar free food are very much popular because of their less calorie content. So food industry uses various artificial sweeteners which are low in calorie content instead of high calorie sugar. Artificial sweeteners/low calorie sweeteners are synthetic sugar substitutes but may be derived from naturally occurring substances, including herbs or sugar itself. The growing consumer interest in health and its relationship with diet has led to a considerable rise in the demand for low calorie fat products. Artificial sweeteners are also known as intense sweeteners because they are many times sweeter than regular sugar. Therefore, it is very important to understand their chemistry in relation to the stability on processing and storage of food products in which these sweeteners are used.
... [7] Thed erivatization of aspar-tame with branched N-alkyl-or N-arylalkyl groups generates even sweeter compounds,such as the more recently approved food additives neotame and advantame (Scheme 1A). [6,[8][9][10] Notably,n eotame is 7000-13 000 times sweeter than sucrose, while advantame is about 20 000 times sweeter than sucrose. Ac ommon synthetic method for neotame and advantame production is the reductive N-alkylation of aspartame with the corresponding aldehyde in the presence of hydrogen using apalladium (Pd/C) or platinum (Pt/C) hydrogenation catalyst (Scheme 1B,M ethod 1). ...
... Ac ommon synthetic method for neotame and advantame production is the reductive N-alkylation of aspartame with the corresponding aldehyde in the presence of hydrogen using apalladium (Pd/C) or platinum (Pt/C) hydrogenation catalyst (Scheme 1B,M ethod 1). [10][11][12][13][14] An alternative strategy for neotame production involves N-(3,3-dimethylbutyl)-l-aspartic acid [l-3a]a saprecursor,w hich is linked to l-phenylalanine methyl ester by amide-bond coupling (Scheme 1B, Method 2). [15][16][17] This precursor is chemically synthesized by reductive N-alkylation of l-aspartic acid (or its ester derivative) using transition-metal catalysts (Pd/C or Pt/C). ...
Article
Full-text available
Aspartic acid derivatives with branched N ‐alkyl or N ‐arylalkyl substituents are valuable precursors to artificial dipeptide sweeteners such as neotame and advantame, which have wide‐ranging applications in the food industry. Despite the potential applications of these amino acid precursors to aspartame‐based sweeteners, the development of a biocatalyst to synthesize these compounds in a single asymmetric step is an as yet unmet challenge. Herein we report an enantioselective biocatalytic synthesis of various difficult N ‐substituted aspartic acids including N ‐(3,3‐dimethylbutyl)‐L‐aspartic acid and N ‐[3‐(3‐hydroxy‐4‐methoxyphenyl)propyl]‐L‐aspartic acid, precursors to neotame and advantame respectively, using an engineered variant of ethylenediamine‐ N , N '‐disuccinic acid (EDDS) lyase from Chelativorans sp. BNC1. This engineered C‐N lyase (mutant D290M/Y320M) displayed a remarkable 1140‐fold increase in activity for the selective hydroamination of fumarate compared to that of the wild‐type enzyme, which could be rationalized from the analysis of crystal structures. These results open up new opportunities to develop practical multienzymatic processes for the more sustainable and step‐economic synthesis of an important class of food additives.
... [7] The derivatization of aspar-tame with branched N-alkyl-or N-arylalkyl groups generates even sweeter compounds, such as the more recently approved food additives neotame and advantame (Scheme 1 A). [6,[8][9][10] Notably, neotame is 7000-13 000 times sweeter than sucrose, while advantame is about 20 000 times sweeter than sucrose. A common synthetic method for neotame and advantame production is the reductive N-alkylation of aspartame with the corresponding aldehyde in the presence of hydrogen using a palladium (Pd/C) or platinum (Pt/C) hydrogenation catalyst (Scheme 1 B, Method 1). ...
... A common synthetic method for neotame and advantame production is the reductive N-alkylation of aspartame with the corresponding aldehyde in the presence of hydrogen using a palladium (Pd/C) or platinum (Pt/C) hydrogenation catalyst (Scheme 1 B, Method 1). [10][11][12][13][14] An alternative strategy for neotame production involves N-(3,3-dimethylbutyl)-l-aspartic acid [l-3 a] as a precursor, which is linked to l-phenylalanine methyl ester by amide-bond coupling (Scheme 1 B, Method 2). [15][16][17] This precursor is chemically synthesized by reductive N-alkylation of l-aspartic acid (or its ester derivative) using transition-metal catalysts (Pd/C or Pt/C). ...
Article
Full-text available
Süß! Das Enzym Ethylendiamin‐N,N′‐Dibernsteinsäure‐Lyase wurde durch strukturgelenkte Mutagenese für die enantioselektive Synthese von anspruchsvollen N‐substituierten Asparaginsäuren optimiert, die wichtige chirale Vorläufer für künstliche Dipeptid‐Süßstoffe wie Neotam und Advantam sind. Diese neu entwickelte C‐N‐Lyase zeigte einen bemerkenswerten 1140‐fachen Anstieg der Aktivität für die selektive Hydroaminierung von Fumarat. Abstract Aspartic acid derivatives with branched N‐alkyl or N‐arylalkyl substituents are valuable precursors to artificial dipeptide sweeteners such as neotame and advantame. The development of a biocatalyst to synthesize these compounds in a single asymmetric step is an as yet unmet challenge. Reported here is an enantioselective biocatalytic synthesis of various difficult N‐substituted aspartic acids, including N‐(3,3‐dimethylbutyl)‐l‐aspartic acid and N‐[3‐(3‐hydroxy‐4‐methoxyphenyl)propyl]‐l‐aspartic acid, precursors to neotame and advantame, respectively, using an engineered variant of ethylenediamine‐N,N′‐disuccinic acid (EDDS) lyase from Chelativorans sp. BNC1. This engineered C–N lyase (mutant D290M/Y320M) displayed a remarkable 1140‐fold increase in activity for the selective hydroamination of fumarate compared to that of the wild‐type enzyme. These results present new opportunities to develop practical multienzymatic processes for the more sustainable and step‐economic synthesis of an important class of food additives.
... Natural and artificial sweeteners differ greatly in their sweetness potency. Natural sweeteners range from 0.1 to 450 times sweeter than sucrose (lactose and monk fruit, respectively), whereas artificial nutritive and nonnutritive sweeteners can be up to 20,000 times as sweet as sucrose (Advantame; Nofre and Tinti, 2000). When addressing sugar and calorie reduction, artificial sweeteners have more desirable taste profiles and when only flavor is considered (blind tasting), foods and beverages sweetened with artificial sweeteners generally score better than natural nonnutritive sweeteners (Morais et al., 2014;Voorpostel et al., 2014;Zorn et al., 2014;Kubica et al., 2015;Rocha and Bolini, 2015). ...
... Lower glycemic index and virtually zero calories (1.5 kcal/g) Successfully produced by lactic acid bacteria Rare in nature and has to be produced artificially using a calcium catalyst 0.92× (Oh, 2007;Patra et al., 2009;Fujimaru et al., 2012;Shankar et al., 2013) Natural (Kim and Kinghorn, 2002;Pawar et al., 2013;Sirshendu et al., 2013;FDA, 2014FDA, , 2015aNarayanan et al., 2014) Rebaudioside A (FDA, 1981(FDA, , 1983Bell and Labuza, 1991;Nofre and Tinti, 2000;Anton et al., 2010;Pandurangan et al., 2014;Kumari et al., 2016;Toniolo and Temussi, 2016) Neotame (Newtame) ...
Article
Sugar overconsumption continues to increase worldwide and contributes to multiple health-related issues. Dairy foods represent a large market, grossing more than $125 billion per year worldwide. Consumer demands for healthier products are leading to a large push for sugar reduction in dairy foods. Sugar plays an important role in dairy foods, not only in flavor but also in texture, color, and viscosity. Replacing sugar can have negative effects, making substitution inherently difficult. Natural and artificial nonnutritive sweeteners exist for sugar reduction. Natural nonnutritive sweeteners are popular, particularly for label appeal, but many consumers still prefer the taste of artificial nonnutritive sweeteners. Sweet taste perception can also be affected by texture of the food matrix and the presence of fat. Other sugar reduction techniques include hydrolysis of lactose, ultrafiltration, and direct reduction. This review will address the role of sugar, alternative sweeteners, and sugar reduction in ice cream, yogurt, and flavored milk.
... Neotame is considered by some to be the successor to aspartame and was approved as a sweetener in 2002 by the FDA (Chattopadhyay et al., 2014, Nofre & Tinti, 2000. Neotame's sweetness is 7,000 to 13,000 times more potent than sucrose, and is sold under the brand name Newtame R (Carocho et al., 2017). ...
... Neotame's sweetness is 7,000 to 13,000 times more potent than sucrose, and is sold under the brand name Newtame R (Carocho et al., 2017). It has a relatively clean sweet taste, with little or no bitter or metallic off-tastes, is stable across a range of pH and temperatures, and is of low cost (Nofre & Tinti, 2000), although some cite a licorice off-taste at higher concentrations that may be considered undesirable (O'Donnell and Kearsley 2012). The temporal properties of neotame still differ from sucrose, with increased lingering sweetness, although it has been substituted for 20% to 30% of sucrose in soft drinks with no perceived difference in taste (Schiffman, Sattely-Miller, & Bishay, 2008). ...
Article
The global rise in obesity, type II diabetes, and other metabolic disorders in recent years has been attributed in part to the overconsumption of added sugars. Sugar reduction strategies often rely on synthetic and naturally occurring sweetening compounds to achieve their goals, with popular synthetic sweeteners including saccharin, cyclamate, acesulfame potassium, aspartame, sucralose, neotame, alitame, and advantame. Natural sweeteners can be further partitioned into nutritive, including polyols, rare sugars, honey, maple syrup, and agave, and nonnutritive, which include steviol glycosides and rebaudiosides, luo han guo (monk fruit), and thaumatin. We choose the foods we consume largely on their sensory properties, an area in which these sugar substitutes often fall short. Here, we discuss the most popular synthetic and natural sweeteners, with the goal of providing an understanding of differences in the sensory profiles of these sweeteners versus sucrose, that they are designed to replace, essential for the effectiveness of sugar reduction strategies. In addition, we break down the influence of these sweeteners on metabolism, and present results from a large survey of consumers' opinions on these sweeteners. Consumer interest in clean label foods has driven a move toward natural sweeteners; however, neither natural nor synthetic sweeteners are metabolically inert. Identifying sugar replacements that not only closely imitate the sensory profile of sucrose but also exert advantageous effects on body weight and metabolism is critical in successfully the ultimate goals of reducing added sugar in the average consumer's diet. With so many options for sucrose replacement available, consumer opinion and cost, which vary widely with suagr replacements, will also play a vital role in which sweeteners are successful in widespread adoption.
... [8] After ingestion of NTM in humans, approximately half of it is eliminated through the feces as 3,3-dimethylbutylaspartylphenylalanine (DMB-Asp-Phe), and approximately half is absorbed as intact NTM, which is afterwards hydrolyzed into DMB-Asp-Phe and MeOH. [9] However, it is similar to aspartame in that 10-12% of it is absorbed as the intake form, [10] and some parts of NTM might also be absorbed without metabolization. ...
Article
In this paper, we have studied the in vitro binding of neotame (NTM), an artificial sweetener, with native calf thymus DNA using different methods including spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD), and viscosimetric techniques. From the spectrophotometric studies, the binding constant (Kb) of NTM-DNA was calculated to be 2 × 10³ M⁻¹. The quenching of the intrinsic fluorescence of NTM in the presence of DNA at different temperatures was also used to calculate binding constants (Kb) as well as corresponding number of binding sites (n). Moreover, the obtained results indicated that the quenching mechanism involves static quenching. By comparing the competitive fluorimetric studies with Hoechst 33258, as a known groove probe, and methylene blue, as a known intercalation probe, and iodide quenching experiments it was revealed that NTM strongly binds in the grooves of the DNA helix, which was further confirmed by CD and viscosimetric studies. In addition, a molecular docking method was employed to further investigate the binding interactions between NTM and DNA, and confirm the obtained results.
... Each NNS is structurally different from the others [54]. In addition to having a range of sweetness intensities, the structural differences lead to different amounts of NNSs absorbed and post-ingestive behaviors [55][56][57][58][59][60][61]. Despite these differences, our results suggest no differential glycemic impact by type of NNS. ...
Article
Background/objectives: Nonnutritive sweeteners (NNSs) are zero- or low-calorie alternatives to nutritive sweeteners, such as table sugars. A systematic review and meta-analysis of randomized controlled trials was conducted to quantitatively synthesize existing scientific evidence on the glycemic impact of NNSs. Subjects/methods: PubMed and Web of Science databases were searched. Two authors screened the titles and abstracts of candidate publications. The third author was consulted to resolve discrepancies. Twenty-nine randomized controlled trials, with a total of 741 participants, were included and their quality assessed. NNSs under examination included aspartame, saccharin, steviosides, and sucralose. The review followed the PRISMA guidelines. Results: Meta-analysis was performed to estimate and track the trajectory of blood glucose concentrations over time after NNS consumption, and to test differential effects by type of NNS and participants' age, weight, and disease status. In comparison with the baseline, NNS consumption was not found to increase blood glucose level, and its concentration gradually declined over the course of observation following NNS consumption. The glycemic impact of NNS consumption did not differ by type of NNS but to some extent varied by participants' age, body weight, and diabetic status. Conclusions: NNS consumption was not found to elevate blood glucose level. Future studies are warranted to assess the health implications of frequent and chronic NNS consumption and elucidate the underlying biological mechanisms.
... Mean values aucrose 75 ± 6 6 ± 2 10 ± 2 9 ± 2 saccharin 69 ± 6 18 ± 5 11 ± 3 27 ± 3 acesulfame 68 ± 3 29 ± 3 7 ± 1 32 ± 3 aspartame 70 ± 3 7 ± 2 5 ± 1 18 ± 3 neotame 73 ± 3 17 ± 3 11 ± 3 32 ± 3 blank 2 ± 1 3 ± 1 3 ± 1 8 ± 1 tinguish clearly between the two tastes. The values of off-flavours obtained in our experiments were moderately higher than those reported by other authors (PRAKASH et al. 2002;NOFRE & TINTI 2000). The probable reason was that in our experiments, the assessors were more concentrated on the evaluation of off-flavours. ...
Article
Sensory profiles of saccharin, acesulfame K, aspartame, and neotame were compared with that of sucrose in three different types of water (tap water, commerical Crystalis water, and distilled water) under the conditions of the respective ISO standards. The intensities of off-flavours, especially bitter and metallic tastes, were higher in the solutions of synthetic sweeteners than in that of sucrose. The aspartame solution was the sample closest to the sucrose solution, and the intensity of off-flavours was significantly higher in acesulfame solution. Ratings of the bitter taste were related to those of the metallic taste, the relation being semilogarithmic. The performancies of different assessors were nearly the same in all ratings, and the absolute values of the ratings of sweetness and different off-flavours had the same repeatabilities. The relative accuracy was, naturally, much higher in off-flavours than in the case of sweetness.
... This attached 3, 3-dimethylbutyl group to aspartic acid block peptidase enzymes in the digestive system to hydrolyze the peptide bond into the two free amino acids aspartic acid and phenyl alanine. This peptidase enzyme resistance makes Neotame safer for individuals with the rare disease of disorder phenylketonuria (PKU) and help manufacturers to eliminate the warning label that the product contains phenyl alanine (13). ...
Article
Full-text available
High Intense-sweeteners (HIS) are commonly used as a sugar substitutes or sugar alternatives and provide sweet without calories. HIS are in high demands due to its multiple advantages including assisting people in losing weight or avoiding obesity and assisting diabetics to control their blood sugar level. The first known intense-sweetener is Saccharine that was discovered in the year 1878. Since then scientists discovered several other intensive sweeteners that are sweater than sucrose with zero calorie. Some discovered sweeteners are Plants extract (Stevoil glycosides, and Mogrosides), semi-synthetic peptides (Aspartame, Neotame, and sucralose), and synthetic chemicals. (Saccharine, Acesulfame-K, and Cyclamate). These High intensive sweeteners have been approved as safe for applications [1] in foods, beverages, dietary supplements, and pharmaceuticals products by Food and Drug administration (FDA) [2] in United States and by other similar agencies in other countries [3]. The levels of these non-nutritive high intensive sweeteners used in foods, beverages, dietary supplements, and pharmaceutical products are based on the approved daily intake (ADI) by FDA and by other safety authorities worldwide. This ADI level is 100 fold lower than the safe dose demonstrated in laboratory studies. It is estimated that the global demand of HIS is exceeding 9.0 billion dollars and growing. The only HIS that is declining in global market is the old discovered sweetener Saccharine.
... Within the rather broad substrate spectrum, we next examined substrates with long aliphatic chains that are precursors of aspartame derivatives. Derivatization of the artificial dipeptide sweetener aspartame with N-alkyl groups can generate even sweeter compounds, such as the approved food additive neotame, which is 7,000-13,000 times sweeter than sucrose 34 . In this study, N-butyl-l-aspartic acid (3f), which is the precursor to neotame analogue, was synthesized on a kilogram scale using whole cells fermented from merely 2 l of medium with excellent conversion (>97%), isolated yield (92%, 1.4 kg) and stereoselectivity (>99% e.e.) (Fig. 4b), demonstrating the great potential of the redesigned AspBs to offer alternative synthetic options for the industrial preparation of valuable ncAA products. ...
Article
Full-text available
Although C–N bonds are ubiquitous in natural products, pharmaceuticals and agrochemicals, biocatalysts forging these bonds with high atom-efficiency and enantioselectivity have been limited to a few select enzymes. In particular, ammonia lyases have emerged as powerful catalysts to access C–N bond formation via hydroamination. However, the use of ammonia lyases is rather restricted due to their narrow synthetic scope. Herein, we report the computational redesign of aspartase, a highly specific ammonia lyase, to yield C–N lyases with cross-compatibility of non-native nucleophiles and electrophiles. A wide range of non-canonical amino acids (ncAAs) are afforded with excellent conversion (up to 99%), regioselectivity >99% and enantioselectivity >99%. The process is scalable under industrially relevant protocols (exemplified in kilogram-scale synthesis) and can be facilely integrated in cascade reactions (demonstrated in the synthesis of β-lactams with N-1 and C-4 substitutions). This versatile and efficient C–N lyase platform supports the preparation of ncAAs and their derivatives, and will present opportunities in synthetic biology. Ammonia lyases are powerful catalysts to access C–N bond formation via hydroamination, but show a narrow synthetic scope. Now, by computational redesign of an aspartase, a C–N lyase is developed that shows cross-compatibility of non-native nucleophiles and electrophiles expanding the synthetic scope.
... The artificial sweetener, aspartame is the chemical agent, N-L-alpha-aspartyl-L-phenylalanine methyl ester (C 14 H 18 N 2 O 5 ). 1 This white, crystalline and odorless powder is 180-200 times sweeter than sucrose. 2 Aspartame is controversially used as an ingredient in more than 6000 foods including chewing gum, desserts, yogurts, vitamins, medicines, and diet beverages. 3 The acceptable daily intake (ADI) of aspartame has been fixed at 40 mg/kg body weight/ day by European food regulatory authorities 4 and at 50 mg/kg body weight/day by the US FDA 5 for all individuals. ...
Article
Full-text available
Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.
... times greater than sucrose and 30-60 times greater than aspartame [1]. While neotame has approximately the same stability as aspartame in the acidic pH range (pH 3-5.5), neotame at neutral pH is significantly more stable than aspartame [2][3][4]. Dimethyl butyl (DMB), contained in the chemical structure of neotame, provides unique properties such as significantly improved sweetening power, flavor-enhancing properties, and stabilization during cooking or pasteurization [5]. The DMB group restricts the reactivity of the dipeptide amino group; therefore, no cyclization occurs unlike aspartame [6]. ...
Article
A selective and simple biosensor was prepared by immobilizing chitosan/nickelnanoparticles/multi‐walled carbon nanotubes biocomposite on the glassy carbon electrode surface for voltammetric quantification of neotame. The biocomposite modified surface (Chi/NiNPs/MWCNTs/GCE) proposed in this study showed good electrocatalytic activity for neotame with an improved voltammetric peak current at 1.004 V. Under optimum conditions, Chi/NiNPs/MWCNTs/GCE gave linear SWV responses at the range of 2 μM ~50 μM for neotame with 0.84 μM determination limit. This voltammetric sensor was successfully employed for the quantification of neotame on food samples. Selective, accurate, and precise determination of neotame highlight the importance of this electrode in monitoring the control of food additives and ensures attract a great deal of attention.
... Regarding safety, neotame, as has been subject to a battery of tests, in which, even at doses higher that its ADI, no toxicity was detected. No adverse findings were reported for physical examinations, water consumption, clinical pathology evaluations, no reports of morbidity, mortality, organ toxicity, macroscopic or microscopic postmortem findings in murine models and other test animals (Mitchell, 2006;Nabors (Part I), 2001;Nofre and Tinti, 2000;Zhu et al., 2016). ...
Article
Sweet has always been a very important basic taste for mankind, although sweetness is always related to either weight gain or teeth decay. Sweeteners entered the food industry back in the 1800's and are now staple in foodstuffs. Despite their long relationship with food, sweeteners have been in the spotlights for many reasons. Since being the perfect choice for diabetics, to the dangers concerning toxicity, cancer and other health issues associated with their consumption, sweeteners have come a long way. The conflicting results for the same sweeteners and the divergent regulations are fuel for a wide debate on the impact of sweeteners in the industry, health and lifestyle of mankind. In this review, the history, main concerns, benefits, disadvantages, classification and future trends are revisited for nutritive, intense and natural food additives, while future perspectives are hypothesized.
... It is far cheaper than sugar and is an attractive option for manufacturers. 4 Aspartame is a synthetic dipeptide formed by the reaction of L-aspartic acid with L-phenylalanine methyl ester. 5 It was first marketed as NutraSweet and Equal and is now freely available in supermarkets. ...
Article
Full-text available
Aspartame is a synthetic dipeptide artificial sweetener, frequently used in foods, medications, and beverages, notably carbonated and powdered soft drinks. Since 1981, when aspartame was first approved by the US Food and Drug Administration, researchers have debated both its recommended safe dosage (40 mg/kg/d) and its general safety to organ systems. This review examines papers published between 2000 and 2016 on both the safe dosage and higher-than-recommended dosages and presents a concise synthesis of current trends. Data on the safe aspartame dosage are controversial, and the literature suggests there are potential side effects associated with aspartame consumption. Since aspartame consumption is on the rise, the safety of this sweetener should be revisited. Most of the literature available on the safety of aspartame is included in this review. Safety studies are based primarily on animal models, as data from human studies are limited. The existing animal studies and the limited human studies suggest that aspar-tame and its metabolites, whether consumed in quantities significantly higher than the recommended safe dosage or within recommended safe levels, may disrupt the oxidant/antioxidant balance, induce oxidative stress, and damage cell membrane integrity, potentially affecting a variety of cells and tissues and causing a deregulation of cellular function, ultimately leading to systemic inflammation.
... Le néotame est formé par la N-alkylation de l'aspartame et a un pouvoir sucrant 30 à 60 fois plus élevé que ce dernier (Nofre and Tinti, 2000). En 2003, l'organisation des Nations unies pour l'alimentation et l'agriculture et l'organisation mondiale de la santé ont fixé la DJA à 2mg/kg/jour (Chakraborty and Das, 2019). ...
Thesis
Les glucides et les édulcorants sont détectés par des récepteurs du goût sucré à la membrane apicale des cellules entéroendocrines (CEE). Ces récepteurs hétérodimères T1R2-T1R3 sont couplés à la protéine G gustducine dont la sous-unité α est codée par le gène GNAT3. L’activation de ces récepteurs entraine une cascade de signalisation conduisant à la sécrétion de GLP-1 par les CEE. Les maladies métaboliques sont associées à des altérations de l’homéostasie glucidique et énergétique. Elles entrainent une diminution de la concentration plasmatique en GLP-1, dont la sécrétion est restaurée après rémission. L’objectif de ma thèse a été d’étudier le rôle de la voie de transduction du goût sucré, et de l’α-gustducine, dans les maladies métaboliques et leur rémission. Les résultats obtenus dans l’intestin montrent que cette voie de signalisation est exprimée spécifiquement dans les CEE. De plus, l’obésité conduit à une altération de cette voie dans les CEE et notamment à une sous-expression de GNAT3 participant au défaut de sécrétion du GLP-1. Dans l’amélioration métabolique après remodelage intestinal, la restauration de la sécrétion de GLP-1 est en partie due à une sur-expression de GNAT3 dans l’anse alimentaire. En revanche, le microbiote intestinal dysbiotique n’a pas d’impact significatif sur l’expression de GNAT3 dans l’obésité. Pour conclure, cette étude montre le rôle de la voie de transduction du goût sucré dans le défaut de sécrétion de GLP-1 dans les maladies métaboliques. L’identification de molécules pouvant stimuler la voie intestinale de transduction du goût sucré permettrait de stimuler la sécrétion endogène de GLP-1 chez les patients obèses avec ou sans diabète.
... Neotame is moderately heat stable, extremely potent, rapidly metabolized, completely eliminated, and does not appear to accumulate in the body. Mice and other test animals fed neotame did not show adverse physical symptoms, water consumption, or clinical pathology evaluations and there were no reports of morbidity, mortality, organ toxicity, or macroscopic or microscopic postmortem findings (31)(32)(33). ...
Article
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The consumption of sugar-free foods is growing because of their low-calorie content and the health concerns about products with high sugar content. Sweeteners that are frequently several hundred thousand times sweeter than sucrose are being consumed as sugar substitutes. Although nonnutritive sweeteners (NNSs) are considered safe and well tolerated, their effects on glucose intolerance, the activation of sweet taste receptors, and alterations to the composition of the intestinal microbiota are controversial. This review critically discusses the evidence supporting the effects of NNSs, both synthetic sweeteners (acesulfame K, aspartame, cyclamate, saccharin, neotame, advantame, and sucralose) and natural sweeteners (NSs; thaumatin, steviol glucosides, monellin, neohesperidin dihydrochalcone, and glycyrrhizin) and nutritive sweeteners (polyols or sugar alcohols) on the composition of microbiota in the human gut. So far, only saccharin and sucralose (NNSs) and stevia (NS) change the composition of the gut microbiota. By definition, a prebiotic is a nondigestible food ingredient, but some polyols can be absorbed, at least partially, in the small intestine by passive diffusion: however, a number of them, such as isomaltose, maltitol, lactitol, and xylitol, can reach the large bowel and increase the numbers of bifidobacteria in humans. Further research on the effects of sweeteners on the composition of the human gut microbiome is necessary. Adv Nutr 2019;10:S31-S48.
... A t-butyl group is added to the free amine group of aspartic acid. This addition adds a second hydrophobic group and results in a product that is 30 to 60 times sweeter than aspartame (Nofre & Tinti, 2000). It is rapidly metabolized by hydrolysis of the methyl ester via esterases present throughout the body. ...
Article
Since their discovery, the safety of artificial sweeteners has been controversial. Artificial sweeteners provide the sweetness of sugar without the calories. As public health attention has turned to reversing the obesity epidemic in the United States, more individuals of all ages are choosing to use these products. These choices may be beneficial for those who cannot tolerate sugar in their diets (e.g., diabetics). However, scientists disagree about the relationships between sweeteners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus. Recently these substances have received increased attention due to their effects on glucose regulation. Occupational health nurses need accurate and timely information to counsel individuals regarding the use of these substances. This article provides an overview of types of artificial sweeteners, sweetener history, chemical structure, biological fate, physiological effects, published animal and human studies, and current standards and regulations.
... When we add the t-butyl group to the free amine group of aspartic acid, it leads to a second hydrophobic group and results in a product that is 30-60 times sweeter than aspartame. [18] Figure 4 shows the synthesis of neotame. ...
Article
Full-text available
Artificial Sweeteners provide the sweetness of natural sugar without the calories and produce a low glycemic response. These sweeteners are used instead of sucrose (table sugar) to sweeten foods and beverages. Consumers and food manufacturers have long been interested in dietary sweeteners to replace sucrose in foods. This article goes into a lot of details about the different types of sweeteners such as saccharin, acesulfame potassium, aspartame, neotame and sucralose, their uses, chemistry and their potential effects on health. These sweeteners form acute and chronic effects on human health.
... Within the rather broad substrate spectrum, we next examined substrates with long aliphatic chains that are precursors of aspartame derivatives. Derivatization of the arti cial dipeptide sweetener aspartame with N-alkyl groups can generate even sweeter compounds, such as the approved food additive neotame, which is 7000-13000 times sweeter than sucrose 31 . In this study, N-butyl-L-aspartic acid (3f), which is the precursor to neotame analog, was synthesized on a kilogram scale using whole cells fermented from merely 2 L medium with excellent conversion (> 97%), isolated yield (92%, 1.4 kg), and stereoselectivity (> 99% e.e.) (Fig. 3D), demonstrating the great potential of the redesigned AspBs to offer alternative synthetic options for the industrial preparation of valuable ncAA products. ...
Preprint
Full-text available
Although C-N bonds are ubiquitous in natural products, pharmaceuticals, and agrochemicals, biocatalysts that forge these bonds with high atom efficiency and enantioselectivity have primarily been limited to a few select enzymes. In particular, the use of ammonia lyases has emerged as a powerful strategy to access C-N bond formation through hydroamination reactions, which has no counterpart in traditional synthetic chemistry. However, the broad utility of ammonia lyases is rather restricted due to their narrow synthetic scope, and the conjugate addition of a matrix of nucleophilic donors to electrophilic acceptors remains a longstanding challenge. Herein, we report the computational redesign of aspartase, a highly specific ammonia lyase, to yield C-N lyases with unprecedented cross-compatibility of nonnative nucleophiles and electrophiles. A wide range of noncanonical amino acids (ncAAs) are afforded with excellent conversion (up to 99%), regioselectivity > 99%, and product enantiomeric excess > 99%, and the process is scalable under industrially relevant protocols (demonstrated in kilogram-scale synthesis). Furthermore, the redesigned enzymes can be facilely integrated in cascade reactions, as we demonstrated the synthesis of β-lactams with different substitution patterns at the N-1 and C-4 positions in a one-pot reaction. This versatile and efficient C-N lyase platform supports the preparation of diverse libraries of ncAAs and their derivatives and will present opportunities in medicinal chemistry and synthetic biology.
... Já a amostra de sorvete adoçado com aspartame apresentou Imax intermediária, diferindo significativamente de todas as demais amostras (p < 0,05). O tempo total de percepção dos estímulos variou amplamente entre os sorvetes, em que as amostras adoçadas com estévia e neotame apresentaram tempos de percepção mais prolongados, o que evidenciou a presença de gosto residual amargo com maior tempo de duração que as demais amostras, em acordo com resultados publicados por Nofre & Tintil (2000). ...
Article
Full-text available
Resumo O sorvete é um produto amplamente consumido e aceito pela população mundial, e, por essa razão, é de grande importância a busca por formulações que possam ser menos calóricas, especialmente com redução ou ausência de sacarose. A determinação do perfil sensorial tempo-intensidade múltiplo (também denominado perfil sensorial dinâmico), associada ao estudo de aceitação, pode ser de grande importância para direcionar estudos e obter informações que possam contribuir com a obtenção de conhecimentos para a indústria de alimentos sobre mudanças de ingredientes e melhoria da qualidade sensorial. O objetivo do presente estudo foi estudar diferentes formulações de sorvetes de chocolate simbiótico, sendo uma adoçada com sacarose e outras sete adoçadas com diferentes edulcorantes (aspartame, sucralose, neotame e estévia com 60%, 80%, 95% e 97% de rebaudiosídeo A), por meio da aplicação de análise tempo-intensidade múltipla, análise de aceitação e verificação da influência da presença da inulina, do L. acidophilus e dos edulcorantes em características físico-químicas do produto. As amostras que apresentaram maior aceitação foram adoçadas com sacarose e sucralose, seguidas por estévia com 95% e 97% de rebaudiosídeo A. Por meio da análise do mapa interno de preferência, foi observada a importância pronunciada do sabor na aceitação das amostras. O edulcorante que possibilitou a obtenção do sorvete de chocolate de baixa caloria simbiótico, sem diferença significativa com o produto adoçado com sacarose em perfil de doçura, amargor e sabor de leite, bem como em aceitação, foi a sucralose. Os sorvetes de aceitação inferior foram adoçados com aspartame, neotame e estévia, provavelmente em razão do gosto amargo mais intenso e com maior tempo de duração (p < 0,05). A Os sorvetes com inulina em sua formulação apresentaram derretimento mais lento quando comparados à amostra sem inulina e formulada com sacarose.
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Oral lichen planus (OLP) is a potentially malignant, chronic inflammatory condition affecting the oral cavity. Most of the patients have associated systemic conditions like hypertension, diabetes mellitus and hyperthyroidism. Patients experience severe burning pain in the oral cavity. Although, the standard treatment for this condition is a corticosteroid, the associated side effects limit its prolonged use. Chronic topical use can lead to mucosal atrophy, secondary candidal infection and burning pain which could ultimately lead to dietary disturbance, psychological problems and negative impact on the quality of life. Therefore, an alternative approach like herbal therapy including neem tree leaves was tried in OLP patients. Aqueous neem leaves extract has anti-inflammatory, immunomodulatory, antifungal and anticancer agents in addition to various antioxidants, which could prove to be beneficial in treating OLP. This paper presents an herbal therapeutics case series of a novel aqueous neem leaves extract mouthwash therapy which was successful in resolving the signs and symptoms of OLP in four patients.
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Flavor peptide refers to small peptides that extracted from food or synthesized by amino acids to enhance, improve, or to cover up the sensory characteristics. The new ultra -high performance liquid chromatography and quadrupole time of flight mass spectrometry have been used for isolation and identification of flavor peptides rapidly and efficiently. This work describes the funtion, isolation, identification, and the latest research of flavor peptide in food to provide a reference for the development of food flavor and its seasoning.
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Background: Sugar is an inevitable part of our diet. Since ages, sweeteners have been used to enhance the flavour and appearance of food products. Sweeteners may be natural or synthetically produced. Those that are synthetic, as a whole, are referred to as artificial sweeteners. This review aims at highlighting the characteristics and health implications of artificial sweeteners. Methodology: In this review, the physical and chemical characteristics of artificial sweeteners are highlighted. Also, the impact of artificial sweeteners on human health is discussed in detail. The data has been collected using standard search engines like PubMed, Google scholar and websites of publishing houses like Elsevier and Springer. Results and Discussion: Today, due to high calorie content, natural sweeteners are getting replaced by artificial ones. The US Food and Drug Administration (USFDA) has approved utilization of five artificial sweeteners namely, saccharin, sucralose, aspartame, neotame and cyclamate. However, artificial sweeteners should be consumed carefully and in limited quantities. This is because the consumption of artificial sweeteners is controversial owing to their effects on health ranging from mild headache to dreadful cancer risks. Conclusion: Hence, long term study of these sweeteners for further safety evaluation on health risks is essential.
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Experimental samples simulated the composition of vermouths. In all experiments, 0.01% quinine was used as a standard bitter substance. Sucrose increased the acceptability in the concentration range of up to 14%, remaining constant at higher concentrations, both in aqueous and 16% ethanolic solutions. A decrease of bitterness was observed in water but not in 16% ethanol. Ethanol did not affect the sweetness appreciably at the concentrations of up to 16%, but 32% ethanolic solutions appeared less sweet. Ethanol enhanced the bitterness only at high concentrations; interactions were similar in the samples containing 10% and 16% sucrose. Aspartame and Neotame sweetness increased the acceptability and decreased the bitterness similarly to sucrose, both in aqueous and in 16% ethanolic solutions.
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No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. It was first approved by the US Food and Drug Administration (FDA) in 1981. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. these metabolites have some health risks specially on PKU (Phenyl Ketone Urea) patients who can’t metabolize the amino acid phenyl alanine. This study aims to investigate the health effects of aspartame on Balb-c mice. 16 Balb-c mice were given physiological solution by oral gavage(control) and the study groups were given the recommended ADI (Acceptable Daily Intake) for mice (ADI = 250mg/kg/body weight) of Aspartame diluted in water for 15days, 30days. Glucose blood level, lipid profile, marker enzymes (ALT.AST.ALP, γGT) and uric acid were determined at the end of the experiment. The results of this study show that oral administration of aspartame (250mg/kg body weight) was correlated to a significant increase in the lipid profile, fasting blood glucose and some marker enzymes and this increase is time related.
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The relationship between chemical structure and gustatory response is discussed in substantial detail for each of the primary tastes: sweet, bitter, umami, salty and sour. Structural formulas, empirical formulas, molecular weights, and gustatory potencies are provided for most stimuli. Chemical structure/gustatory response reviews are preceded by reviews of current understandings of the biochemical pathways which mediate these gustatory experiences. The relationship between chemical structure and sweet taste is very broad ranging from the common carbohydrates to synthetic sweeteners to natural non-caloric sweeteners and even to some minerals which exhibit sweet taste. The relationship between chemical structure and bitter taste is even more diverse covering essentially all structural classes of organic and inorganic compounds. On the other hand, structures of chemical compounds which exhibit umami taste are narrowly tuned around the structure of monosodium glutamate, the prototypical umami taste compound. This is also true for salty and sour tastes where chemical structures of compounds exhibiting these tastes are all salts and acids, respectively.
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During the last two decades, great effort has been put into research on taste chemoreception. One of many aims is the synthetic production of gustatory compounds more beneficial to health, i.e., the discovery of low- or no-calorie food ingredient products. This is of particular relevance, as parts of western society are overindulging in food, while conversely and regrettably, malnutrition is on the rise in Third World countries. In the latter case, it is necessary to ask how to improve the characteristics of energy-rich but not particularly tasty foods (e.g., soya) in such a fashion that their consumption becomes pleasurable. Gustatory compounds are of equal importance when blended with medication to counteract their predominantly bitter taste. Therefore, our knowledge of the mechanisms of taste receptors is very important.
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The development of neotame, a high-intensity sweetener and flavor enhancer, and its characteristics and potential uses were discussed. The methods of production, stability, and functionality, delivery forms and benefits of the product were also presented. The sweetener received approval by the Food and Drug Administration for use in foods and beverages in the United States. It was found safe for use by children, pregnant women and diabetic patients. It was metabolized by de-esterification, which ensured its complete elimination after digestion.
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Several studies report the effects of excessive use of sugars and sweeteners in the diet. These include obesity, cardiac diseases, diabetes, and even lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus. On the other hand, each sugar and sweetener has a distinct metabolic assimilation process, and its chemical structure plays an important role in this process. Several scientific papers present the biological effects of the sugars and sweeteners in relation to their chemical structure. One important issue dealing with the sugars is the degree of similarity in their structures, focusing mostly on optical isomerism. Finding and developing new sugars and sweeteners with desired properties is an emerging research area, in which in silico approaches play an important role.
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Charge-transfer (CT) interaction of two artificial sweeteners, aspartame (Asp) and neotame (Neo), with three organic π-acceptors was investigated by UV–visible and Infrared (IR) spectrophotometric measurements. The target sweeteners interacted with the 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), chloranilic acid (CA), and picric acid (PA) molecules in methanol solvent at room temperature. Spectral results suggest that the unshared electron pair of nitrogen atoms (-NH2 in Asp molecule, and -NH in Neo molecule) donate electronic charge to the aromatic ring of the acceptor (Asp→acceptor; Neo → acceptor) forming the CT complex via a n → π* transition. The 1:1 Benesi-Hildebrand method was used to calculate several spectroscopic data, such as the formation constant (KCT) and the molar extinction coefficient (εmax), and other physical parameters. The correlation test indicates strong relationships among several of the physical parameters.
Chapter
Synopsis The relationship between chemical structure and gustatory response is discussed in substantial detail for each of the primary tastes: sweet, bitter, umami, salty and sour. Structural formulas, empirical formulas, molecular weights, and gustatory potencies are provided for most stimuli. Chemical structure/gustatory response reviews are preceded by reviews of current understandings of the biochemical pathways which mediate these gustatory experiences. The relationship between chemical structure and sweet taste is very broad ranging from the common carbohydrates to synthetic sweeteners to natural non-caloric sweeteners and even to some minerals which exhibit sweet taste. The relationship between chemical structure and bitter taste is even more diverse covering essentially all structural classes of organic and inorganic compounds. On the other hand, structures of chemical compounds which exhibit umami taste are narrowly tuned around the structure of monosodium glutamate, the prototypical umami taste compound. This is also true for salty and sour tastes where chemical structures of compounds exhibiting these tastes are all salts and acids, respectively.
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Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.
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Objective: Two experiments were conducted to investigate the effects of dietary sucralose on diet preference and growth performance of weaned piglets, and a third experiment was a 28-d safety study to examine if high-dose sucralose could affect the health state of weaned piglets. Methods: In experiment one, 48 piglets had free access to a corn-soybean based diet and the same diet supplemented with 150 mg/kg sucralose for 15 d. In experiment two, 180 piglets were blocked into 5 treatments with 6 replications. They were fed basal diets supplemented with 0, 75, 150, 225, and 300 mg/kg sucralose for 28 days. In experiment three, 108 piglets were randomly assigned to 3 treatments and fed diets supplemented with 0, 150 (suitable level), and 1,500 (ten-fold suitable level) mg/kg sucralose for 28 d. Results: The experiment 1 showed that piglets preferred (p < 0.05) diets containing sucralose during experimental period. In experiment 2, piglets fed a diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than pigs in the control group and other treatment groups during the experiment period. The concentrations of sucralose over 150 mg/kg may decrease feed intake. However, no difference in feed conversion ratio was observed. In experiment 3, piglets fed diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than that of pigs in the control group and 1500 mg/kg treatment groups during the experiment period. Clinical blood metabolites, organ index and histological morphology were not significantly different between sucralose treatments. Conclusion: Sucralose can promote feed intake and thereby improve growth performance of weaned piglets. Moreover, inclusion of 1,500 mg/kg sucralose was demonstrated to have no observed adverse effects. Supplementing 150 mg/kg sucralose for weaned piglets is recommended in this study.
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Introduction to sweeteners Properties of sweeteners Intense sweeteners in foods Bulk food sweeteners Quality assurance and quality control Analytical methods References Further reading
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Sweeteners are classified into two basic categories: nutritive and nonnutritive. Nutritive sweeteners include sugars, sugar alcohols, corn syrups, and high-fructose corn syrups. Nonnutritive sweeteners include acesulfame K, sucralose, and neotame. Most nutritive sweeteners are obtained from plant sources, and nonnutritive sweeteners are synthetic. However, stevioside, a sweet diglycoside extracted from the wild plant Stevia rebaudiana, is noncaloric. Aspartame is a synthetic but low-caloric sweetener.
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The objective of this study was to evaluate the sensory profile and the influence of the information on the acceptance of the symbiotic chocolate ice cream made with sucrose and different sweeteners (aspartame, sucralose, neotame, Stevia with 60%, 85%, 95%, and 97% of rebaudioside A) through analysis of variance (ANOVA), Tukey's test, and partial least of square (PLS) regression. Quantitative descriptive analysis (QDA) was carried out by 18 assessors, who evaluated the samples in relation to the raised descriptors. Additionally, two acceptance tests (blind/informed) were performed with 120 consumers. The samples sweetened with sucralose and rebaudioside 97% presented similar profile to the control sample, thus having a better potential to replace sucrose in chocolate ice cream. The acceptance test carried out with information had higher scores for the attributes appearance, aroma, flavor, texture, and overall impression. The correlation between data from the acceptance tests and QDA showed that the descriptors “low‐energy” and “natural sweetener” claims interfered negatively in the drivers of liking of chocolate ice cream. Therefore, we can conclude that some characteristics unnoticed by consumers were highlighted after providing the information about the product's characteristics. Practical Application This research is important and contributes to the manufacture and development of low‐calorie chocolate ice cream with functional properties, guiding, through suitable sensory and statistical tools, the application of stevia and other artificial sweeteners in products with reduction or total absence of sucrose and highlighting the impact of the labeling of these products on consumer perception.
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Cu–Ni/γ-Al2O3 bimetallic catalysts were developed for anaerobic dehydrogenation of non-activated primary aliphatic alcohols to aldehydes. Systematic investigation about the promotion effect of nickel on the catalytic performance was carried out. Hydrogenation of C=C bond rather than C=O bond, was significantly improved over Cu–Ni/γ-Al2O3 catalyst by introducing nickel, which interprets the good conversion of primary aliphatic alcohols. This work would contribute to design new catalysts for dehydrogenation of primary aliphatic alcohols.
Article
Although there has been increased interest in the use of time-intensity (T-I) measures in sensory studies, there are weaknesses in existing methods for the analysis and presentation of T-I data. This paper reviews the methods for averaging time—intensity curves, pointing out their limitations. A new method is proposed, in which normalization of individual curves is carried out for both intensity and time, and the resulting mean curve is unique. The method accommodates intensity plateaus, non-zero endpoints and non-monotonic curves. The main parameters of the mean curves are averages of the corresponding parameters of the individual curves.
Article
Time-intensity (TI) sweetness curves were generated and ten TI parameters were determined for selected carbohydrate and high potency sweeteners. Samples were evalutated by trained panelists at 5% sucrose equivalency (SEV) in water for sucralose, sucrose, fructose, aspartame, cyclamate, acesulfame-K and saccharin and at 9% SEV in water and a buffered model beverage system for sucralose, sucrose, fructose, aspartame and cyclamate. When compared within each system, differences in temporal properties appeared to be concentration and media dependent. No differences in onset characteristics were observed among equisweet groups. Aftertaste characteristics differed among sweeteners only .at 9% SEV in water where high potency sweeteners tended to have somewhat longer aftertaste than nutritive sweeteners.
Article
This investigation compared the sweet and bitter taste characteristics of aspartame, acesulfame K, and alitame at equisweetness levels with 10% sucrose/water solutions at 22°C using the time-intensity (T-I) sensory technique. Alitame was comparable to sucrose in all taste characteristics. Aspartame had similar taste characteristics to sucrose with the exception of having greater sweet intensities with longer duration (P<0.001) following sample expectoration. Acesulfame K differed remarkably from sucrose. The sweet attribute of acesulfame K appeared quickly (P<0.05) before sample expectoration. This was followed by a moderately intense and lingering bitter character (P< 0.001) which reached maximum intensity after sample expectoration.
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Crossflow microfiltration has become an established process for the separation of microparticles, bacteria and emulsion droplets in a variety of biotechnical applications. After the characterization of microporous membranes and explanation of the different microfiltration processes including the backpulse system, some applications in the biotechnical industry will be discussed in more detail. Special attention will be paid to the sterile filtration, cell mass retention, diafiltration and bubble-free gassing.
Article
Sweeteners are widely used in the food and pharmaceutical industry. The purpose of this paper is to review our current knowledge of sweet taste from chemical, biochemical, electrophysiological, psychophysical, and psychological points of view. The most common sweetners likely to be used in food and pharmaceuticals will be examined in detail. First, the chemical structures of sweet compounds including saccharides, diterpene glycosides, polyols, amino acids, dipeptides, and other nonsugars will be discussed. Second, biochemical approaches to understanding sweetner receptors will be reviewed. Third, electrophysiological and behavioral approaches to understanding sweetner receptors will be discussed. Fourth, psychophysical studies in humans will be shown to be consistent with biochemical and neurophysiological data. In addition, the basic mechanisms of sweet taste revealed by psychophysical studies will be given, including the role of multiple receptor sites, hydrogen bonding, and sodium transport. Finally, the factors that affect preference for sweet taste including the psychological and physiological variables associated with sweet preference will be explored.
Article
After the consumption of fruit, the concentration of methanol in the human body increases by as much as an order of magnitude. This is due to the degradation of natural pectin (which is esterified with methyl alcohol) in the human colon. In vivo tests performed by means of proton-transfer-reaction mass spectrometry show that consumed pectin in either a pure form (10 to 15 g) or a natural form (in 1 kg of apples) induces a significant increase of methanol in the breath (and by inference in the blood) of humans. The amount generated from pectin (0.4 to 1.4 g) is approximately equivalent to the total daily endogenous production (measured to be 0.3 to 0.6 g/day) or that obtained from 0.3 liters of 80-proof brandy (calculated to be 0.5 g). This dietary pectin may contribute to the development of nonalcoholic cirrhosis of the liver.
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N-(3,3-Dimethylbutyl)-L-aspartyl-D± a-aminoalkanoic acid N-(S)-1-phenyl-1-alkanamide useful as a sweetening agent
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