Jennifer Littlechild

Jennifer Littlechild
University of Exeter | UoE · Department of Biosciences

About

240
Publications
21,003
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Introduction
Skills and Expertise
Additional affiliations
October 2015 - present
University of Exeter
Position
  • Professor of Biological Chemistry

Publications

Publications (240)
Article
Full-text available
The biosynthesis of metabolites from available starting materials is becoming an ever important area due to the increasing demands within the life science research area. Access to metabolites is making essential contributions to analytical, diagnostic, therapeutic and different industrial applications. These molecules can be synthesized by the enzy...
Article
Full-text available
In their Editorial for the Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry, Guest Editors Andrés Alcántara, Pablo Domínguez de María, Jennifer Littlechild, and Roland Wohlgemuth and their co‐workers on the European Society of Applied Biocatalysis’ (ESAB) Working Group on Sustainable Chemistry Martin Schürmann and Roger Shel...
Article
The Front Cover shows the treasure box of biocatalysis, which can now be considered as a key enabling technology for the development of sustainable chemistry. The implementation of biocatalytic syntheses in modern chemistry for different industrial sectors has been accelerated by advances and breakthroughs in understanding structure, function, disc...
Article
Invited for this month′s cover is the Working Group Sustainable Chemistry of the European Society of Applied Biocatalysis (ESAB). The image shows the significant contributions of Biocatalysis to science, industry, society, and environment as a technology of first choice for Sustainable Chemistry in the 21st century. The Perspective itself is availa...
Article
The role and power of biocatalysis in sustainable chemistry has been continuously brought forward step by step to its present outstanding position. The problem‐solving capabilities of biocatalysis have been realized by numerous substantial achievements in biology, chemistry and engineering. Advances and breakthroughs in the life sciences and interd...
Article
Full-text available
Osmolytes protect microbial cells against temperature, osmolarity and other stresses. The osmolyte cyclic 2,3-diphosphoglycerate, originally isolated from the thermophilic archaeon Methanothermus fervidus, naturally protects cellular proteins under extreme conditions. The biosynthetic pathway for cyclic 2,3-diphosphoglycerate has been introduced in...
Article
Full-text available
A novel D-lyxose isomerase has been identified within the genome of a hyperthermophilic archaeon belonging to the Thermofilum species. The enzyme has been cloned and over-expressed in Escherichia coli and biochemically characterised. This enzyme differs from other enzymes of this class in that it is highly specific for the substrate D-lyxose, showi...
Article
Lipolytic enzymes are essential biocatalysts in food processing as well as pharmaceutical and pesticide industries, catalyzing the cleavage of ester bonds in a variety of acyl chain substrates. Here, we report the crystal structure of an esterase from the deep-sea hydrothermal vent of the East Pacific Rise (EprEst). The X-ray structure of EprEst in...
Article
Full-text available
Early detection is critical to the successful treatment of life-threatening infections caused by fungal pathogens, as late diagnosis of systemic infection almost always equates with a poor prognosis. The field of fungal diagnostics has some tests that are relatively simple, rapid to perform and are potentially suitable at the point of care. However...
Article
The removal of carbon dioxide from the waste streams of industrial processes is a major challenge for creation of a sustainable circular economy. This makes the synthesis of formate from CO2 by NAD⁺ dependent formate dehydrogenases (FDHs) an attractive process for this purpose. The efficiency of this reaction is however low and to achieve a viable...
Article
Full-text available
A novel transketolase has been reconstituted from two separate polypeptide chains encoded by a ‘split-gene’ identified in the genome of the hyperthermophilic bacterium, Carboxydothermus hydrogenoformans. The reconstituted active α2β2 tetrameric enzyme has been biochemically characterized and its activity has been determined using a range of aldehyd...
Article
The Arabidopsis thaliana BON1 gene product is a member of the evolutionary conserved eukaryotic calcium‐dependent membrane‐binding protein family. The copine protein is composed of two C2 domains (C2A and C2B) followed by a vWA domain. The BON1 protein is localized on the plasma membrane and is known to suppress the expression of immune receptor ge...
Article
Biocatalysis, the use of enzymes in chemical transformations, is an important green chemistry tool. Cascade reactions combine different enzyme activities in a sequential set of reactions. Cascades can occur within a living (usually bacterial) cell; in vitro in 'one pot' systems where the desired enzymes are mixed together to carry out the multi-enz...
Article
Full-text available
Multi‐step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi‐step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of charact...
Article
The phosphate starvation response 1 (PHR1) protein has a central role in mediating the response to phosphate starvation in plants. PHR1 is composed of a number of domains including a MYB domain involved with DNA‐binding and a coiled‐coil domain proposed to be involved with dimer formation. PHR1 binds to the promoter of phosphate starvation‐induced...
Preprint
Full-text available
Multi-step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi-step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of charact...
Article
Full-text available
Sigma class GST (Prostaglandin D synthase), FhGST-S1, is present in the excretory–secretory products (ES) of the liver fluke parasite Fasciola hepatica as cargo of extracellular vesicles (EVs) released by the parasite. FhGST-S1 has a well characterised role in the modulation of the immune response; a key fluke intercession that allows for establish...
Article
Full-text available
Two new thermophilic branched chain amino acid transaminases have been identified within the genomes of different hyper-thermophilic archaea, Geoglobus acetivorans, and Archaeoglobus fulgidus. These enzymes belong to the class IV of transaminases as defined by their structural fold. The enzymes have been cloned and over-expressed in Escherichia col...
Article
Full-text available
A novel type 1 geranylgeranyl pyrophosphate synthase GACE1337 has been identified within the genome of a newly identified hyperthermophilic archaeon Geoglobus acetivorans. The enzyme has been cloned and over-expressed in Escherichia coli. The recombinant enzyme has been biochemically and structurally characterized. It is able to catalyze the synthe...
Article
Full-text available
Two novel epoxide hydrolases (EHs), Sibe-EH and CH65-EH, were identified in the metagenomes of samples collected in hot springs in Russia and China, respectively. The two α/β hydrolase superfamily fold enzymes were cloned, over-expressed in Escherichia coli, purified and characterized. The new EHs were active toward a broad range of substrates, and...
Article
Novel hydrolases from hot and other extreme environments showing appropriate performance and/or novel functionalities, and new approaches for their systematic screening are of great interest for developing new processes, for improving safety, health and environment issues. Existing processes could benefit as well from their properties. The workflow...
Article
The generation of 3-nitrotyrosine, within proteins, is a post-translational modification resulting from oxidative or nitrative stress. It has been suggested that this modification could be used as a biomarker for inflammatory diseases. Despite the superiority of mass spectrometry-based determinations of nitrotyrosine, in a high-throughput clinical...
Article
Full-text available
We would like to comment on recent work published in your journal in October 2016 by Willetts A. et al. [1].[...].
Article
Full-text available
To obtain new insights into community compositions of hyperthermophilic microorganisms, defined as having optimal growth temperatures of 80 °C and above, sediment and water samples were taken from two shallow marine hydrothermal vents (I and II) with temperatures of 100 °C at Vulcano Island, Italy. A combinatorial approach of denaturant gradient ge...
Article
Full-text available
The speed of sequencing of microbial genomes and metagenomes is providing an ever increasing resource for the identification of new robust biocatalysts with industrial applications for many different aspects of industrial biotechnology. Using ‘natures catalysts’ provides a sustainable approach to chemical synthesis of fine chemicals, general chemic...
Article
Full-text available
Thermomyces lanouginosa lipase has been used to develop improved methods for carrier-free immobilization, the Cross-Linked Enzyme Aggregates (CLEAs), for its application in detergent products. An activator step has been introduced to the CLEAs preparation process with the addition of Tween 80 as activator molecule, in order to obtain a higher numbe...
Patent
A liquid detergency composition comprising: protease and non-protease enzyme wherein at least part of either the protease or the non-protease enzyme is cross- linked enzyme aggregate
Patent
A liquid detergency composition comprising a protease and a lipase, wherein the lipase comprises a polypeptide having an amino acid sequence which has at least 90 percent sequence identity with the wild-type lipase derived from Humicola lanuginosa strain DSM 4109 and, compared to said wild-type lipase, comprises a substitution of an electrically ne...
Patent
A process for the manufacture of cross-linked enzyme aggregates comprising the steps of: 1) providing a liquid mixture of the enzyme; 2) precipitating the enzyme comprised by the liquid mixture; 3) cross-linking the enzyme by addition of a cross-linking agent, having at least two reactive groups suitable for cross-linking amino acids; 4) stopping t...
Article
Full-text available
Carboxylic acid reductase enzymes (CARs) meet the demand in synthetic chemistry for a green and regio-specific route to aldehydes from their respective carboxylic acids. However, relatively few of these enzymes have been characterized. A sequence alignment with members of the ANL superfamily of enzymes shed light on CAR functional dynamics. Using a...
Article
Full-text available
A new carboxyl esterase, AF-Est2, from the hyperthermophilic archaeon Archaeoglobus fulgidus has been cloned, over-expressed in Escherichia coli and biochemically and structurally characterized. The enzyme has high activity towards short- to medium-chain p-nitrophenyl carboxylic esters with optimal activity towards the valerate ester. The AF-Est2 h...
Article
Full-text available
With the ultimate goal of identifying robust cellulases for industrial biocatalytic conversions, we have isolated and characterized a new thermostable and very halotolerant GH5 cellulase. This new enzyme, termed CelDZ1, was identified by bioinformatic analysis from the genome of a polysaccharide-enrichment culture isolate, initiated from material c...
Article
Full-text available
A carboxyl esterase (TtEst2) has been identified in a novel thermophilic bacterium, Thermogutta terrifontis from the phylum Planctomycetes and has been cloned and over-expressed in Escherichia coli. The enzyme has been characterized biochemically and shown to have activity toward small p-nitrophenyl (pNP) carboxylic esters with optimal activity for...
Article
Full-text available
This article will discuss the importance of specific extremophilic enzymes for applications in industrial biotechnology. It will specifically address those enzymes that have applications in the area of biocatalysis. Such enzymes now play an important role in catalyzing a variety of chemical conversions that were previously carried out by traditiona...
Article
Full-text available
The three-dimensional structures of the native enzyme and the FMN complex of the overexpressed form of the oxygenating component of the type II Baeyer–Villiger 3,6-diketocamphane monooxygenase have been determined to 1.9 Å resolution. The structure of this dimeric FMN-dependent enzyme, which is encoded on the large CAM plasmid of Pseudomonas putida...
Article
Full-text available
The three-dimensional structures of the native enzyme and the FMN complex of the overexpressed form of the oxygenating component of the type II Baeyer– Villiger 3,6-diketocamphane monooxygenase have been determined to 1.9 A˚ resolution. The structure of this dimeric FMN-dependent enzyme, which is encoded on the large CAM plasmid of Pseudomonas puti...
Article
Full-text available
Archaeal enzymes are playing an important role in industrial biotechnology. Many representatives of organisms living in "extreme" conditions, the so-called Extremophiles, belong to the archaeal kingdom of life. This paper will review studies carried by the Exeter group and others regarding archaeal enzymes that have important applications in commer...
Article
A carboxyl esterase (TtEst) has been identified in a novel thermophilic bacterium, Thermogutta terrifontis from the phylum Planctomycetes and has been cloned and over-expressed in Escherichia coli. The enzyme has been characterised biochemically and shown to have activity towards small p-nitrophenyl (pNP) carboxylic esters with optimal activity for...
Article
The epoxide hydrolases (EHs) represent an attractive option for the synthesis of chiral epoxides and 1,2 diols which are valuable building blocks for the synthesis of several pharmaceutical compounds. A metagenomic approach has been used to identify two new members of the atypical EH limonene-1,2-epoxide hydrolase (LEHs) family of enzymes. These tw...
Data
Full-text available
The phosphotriesterase-like lactonase (PLL) encoded by Vmut_2255 in the hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia (VmutPLL), represents the only hyperthermophilic PLL homologue identified so far in addition to the previously characterized thermophilic PLLs from Sulfolobus spp. The Vmut_2255 gene was cloned, heterologously express...
Chapter
Many natural compounds are halogenated and the enzymes that carry out these reactions have been characterized. This chapter provides a brief overview of the different types of halogenating enzymes characterized to date and their differing structures. It concentrates specifically on the vanadium haloperoxidases with regard to their structure and mec...
Article
Full-text available
Carbonic anhydrase enzymes catalyse the reversible hydration of carbon dioxide to bicarbonate. A thermophilic Thermovibrio ammonificans α-carbonic anhydrase (TaCA) has been expressed in Escherichia coli and structurally and biochemically characterized. The crystal structure of TaCA has been determined in its native form and in two complexes with bo...
Article
Full-text available
A wide range of methods are currently available for determining the dissociation constant between a protein and interacting small molecules. However, most of these require access to specialist equipment, and often require a degree of expertise to effectively establish reliable experiments and analyze data. Differential scanning fluorimetry (DSF) is...
Article
A putative haloalkane dehalogenase has been identified in a marine Rhodobacteraceae and subsequently cloned and over-expressed in Escherichia coli. The enzyme has highest activity towards the substrates 1,6-dichlorohexane, 1-bromooctane, 1,3-dibromopropane and 1-bromohexane. The crystal structures of the enzyme in the native and product bound forms...
Article
Full-text available
During the last decade the use of transaminases for the production of pharmaceutical and fine chemical intermediates has attracted a great deal of attention. Transaminases are versatile biocatalysts for the efficient production of amine intermediates and many have (S)-enantiospecificity. Transaminases with (R)-specificity are needed to expand the a...
Chapter
This chapter will discuss the application of enzymes to carry out biotransformation reactions for the synthesis of building blocks of new drugs within the fine chemicals industry. It will concentrate on the marine environment to discover novel enzymes that have applications in this important area of substainable chemistry. Marine enzymes that have...
Chapter
This chapter covers the general features of protein structure and recent advances in structural bioinformatics. The importance of the three-dimensional structure of the protein target in order to understand its mechanism of action as an aid for drug design is illustrated by specific examples of enzyme inhibition, receptor interactions and drugs bin...
Article
Cytochrome b5 is a ubiquitous electron transport protein. The sequenced viral OtV-2 genome, which infects Ostreococcus tauri, was predicted to encode a putative cytochrome b5 enzyme. Using purified OtV-2 cytochrome b5 we confirm this protein has identical spectral properties to purified human cytochrome b5 and additionally that the viral enzyme can...
Article
The recombinant l-haloacid dehalogenase from the marine bacterium Psychromonas ingrahamii has been cloned and over-expressed in Escherichia coli. It shows activity towards monobromoacetic (100 %), monochloroacetic acid (62 %), S-chloropropionic acid (42 %), S-bromopropionic acid (31 %), dichloroacetic acid (28 %) and 2-chlorobutyric acid (10 %), re...
Data
##Assembly-Data-START## Assembly Method :: Velvet v. 0.7.63 Sequencing Technology :: Illumina ##Assembly-Data-END##
Article
Full-text available
The crystal structures and inhibitor complexes of two industrially important ω-aminotransferase enzymes from Pseudomonas aeruginosa and Chromobacterium violaceum have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however,...
Chapter
Considerable interest has been generated in the mechanism which nature utilises to increase the stability of enzymes found in thermophilic and hyperthermophilic species. This has been the subject of many reviews, and our understanding has been enhanced by the increasing number of high-resolution thermostable enzyme structures that have been determi...
Article
The putative L-haloacid dehalogenase gene (DehRhb) from a marine Rhodobacteraceae family has been cloned and over-expressed in Escherichia coli. The DehRhb protein was shown to be an L-haloacid dehalogenase with highest activity towards brominated substrates with short carbon chains (≤C3). The optimal temperature for enzyme activity is 55ºC and the...
Book
The existence of life at high temperatures is quiet fascinating. At elevated temperatures, only microorganisms are capable of growth and survival. Many thermophilic microbial genera have been isolated from man-made (washing machines, factory effluents, waste streams and acid mine effluents) and natural (volcanic areas, geothermal areas, terrestrial...