Guo-Qiang Chen

Guo-Qiang Chen
Tsinghua University | TH · School of Life Sciences

Professor
Microbial synthetic biology

About

501
Publications
240,069
Reads
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29,098
Citations
Additional affiliations
September 2003 - September 2008
Shantou University
Position
  • Managing Director
October 1994 - present
Tsinghua University
Position
  • Professor (Full)

Publications

Publications (501)
Article
Full-text available
Background Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of...
Article
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Despite its greener credentials, biomanufacturing remains financially uncompetitive compared with the higher carbon emitting, hydrocarbon-based chemical industry. Replacing traditional chassis such as E. coli with novel robust organisms, are a route to cost reduction for biomanufacturing. Extremophile bacteria such as the halophilic Halomonas bluep...
Article
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Hydrogels are used in vascular tissue engineering because of their good biocompatibility. However, most natural hydrogels exhibit high swelling ratio, poor mechanical stability, and low durability, which are key limitations for wider applications. Amphiphilic and fatigue-resistant organohydrogels were fabricated here via the click chemical reaction...
Article
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The hierarchical three-dimensional (3D)-printing scaffolds based on microbial polyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) were designed and used for bone tissue engineering via surface functionalization on 3D-printed (P34HB) scaffolds using polydopamine (PDA)-mediated recombinant human bone morphogenetic protein-2 (BMP2), leading...
Article
Polyhydroxyalkanoates (PHAs) are microbial polyesters that have the potential to replace nonbiodegradable petroplastics. A real-time in situ PHA quantification method has long been awaited to replace the traditional method, which is time- and labor-consuming. Quantification of PHA in living cells was finally developed from fluorescence intensities...
Article
Full-text available
Halomonas bluephagenesis, a haloalkaliphilic bacterium and native polyhydroxybutyrate (PHB) producer, is a non-traditional bioproduction chassis for the next generation industrial biotechnology (NGIB). A single-sgRNA CRISPR/Cas9 genome editing tool is optimized using dual-sgRNA strategy to delete large DNA genomic fragments (>50 kb) with efficiency...
Article
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Protein‐based condensates have been proposed to accelerate biochemical reactions by enriching reactants and enzymes simultaneously. Here, we engineered those condensates into a Photo–Activated Switch in E. coli (PhASE) to regulate enzymatic reactions via tuning the spatial correlation of enzymes and substrates. In this system, scaffold proteins und...
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Halomonas bluephagenesis, a robust and contamination-resistant microorganism has been developed as a chassis for “Next Generation Industrial Biotechnology”. The non-model H. bluephagenesis requires efficient tools to fine-tune its metabolic fluxes for enhanced production phenotypes. Here we report a highly efficient gene expression regulation syste...
Article
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Ligand-induced system plays an important role for microbial engineering due to its tunable gene expression control over timings and levels. An oleic acid (OA)-induced system was recently constructed based on protein FadR, a transcriptional regulator involved in fatty acids metabolism, for metabolic control in Escherichia coli. In this study, we con...
Article
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Halomonas bluephagenesis has been engineered to produce flexible copolymers P34HB or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) from glucose and petrol-chemical precursor, γ-butyrolactone. Herein, gene cluster aldD-dhaT was constructed in recombinant H. bluephagenesis for catalyzing 1,4-butanediol (BDO) into 4-hydroxybutyrate, which could grow to...
Article
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Polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible plastics with potential to replace petroleum based plastics. Diversity of PHA monomer structures provides flexibility in material properties to suit more applications. In this study, 5-hydroxyvalerate (5HV) synthesis pathway was established based on intrinsic alcohol/aldehy...
Article
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Cadaverine, a derivative of l-lysine, has been used as a monomer for the synthesis of bio-based nylon-5,6. This study engineered Halomonas bluephagenesis TD1.0 by blocking the feedback inhibition, overexpressing the key l-lysine synthesis genes, strengthening the l-lysine export system and increasing the supply of oxaloacetate for production of l-l...
Article
Full-text available
Polyhydroxyalkanoates (PHA) are a promising and sustainable alternative to the petroleum-based synthetic plastics. Regulation of PHA synthesis is receiving considerable importance as engineering the regulatory factors might help developing strains with improved PHA-producing abilities. PHA synthesis is dedicatedly regulated by a number of regulator...
Article
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Bacterial outer membrane (OM) is a self-protective and permeable barrier, while having many non-negligible negative effects in industrial biotechnology. Our previous studies revealed enhanced properties of Halomonas bluephagenesis based on positive cellular properties by OM defects. This study further expands the OM defect on membrane compactness b...
Article
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This article introduces the EU Horizon 2020 research project MIX-UP, "Mixed plastics biodegradation and upcycling using microbial communities". The project focuses on changing the traditional linear value chain of plastics to a sustainable, biodegradable based one. Plastic mixtures contain five of the top six fossil-based recalcitrant plastics [pol...
Article
The present study tested the outdoor cultivation of Haloferax mediterranei for PHA production from green macroalgae Ulva sp. in pneumatically agitated bioreactors and applied ultrasonic separation for enhanced settling of archaeal cells. Scaled-up cultivation (40 L) yielded maximum biomass productivity of 50.1 ± 0.11 mg⋅L-1⋅h− 1 with a PHA producti...
Article
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Inflammatory bowel disease and colorectal cancer are common diseases without effective prevention approach. 3-Hydroxybutyrate (3HB) reported to have multiple functions as an oral food supplement, is a small endogenous molecule of our ketone bodies. This study observes that 3HB cures mouse colitis and reduces their colorectal carcinogenesis. The mec...
Article
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Microbial polyhydroxyalkanoates (PHA) containing short- and medium/long-chain-length monomers, abbreviated as SCL-co-MCL/LCL PHAs, generate suitable thermal and mechanical properties. However, SCL-co-MCL/LCL PHAs with carbon chain longer than nine are difficult to synthesize due to the low specificity of PHA synthase PhaC and the lack of either SCL...
Article
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The development of biofouling is a major problem for marine industries. The conception of antifouling and fouling release coatings, with controlled physical-chemical properties is a promising strategy. Among them, amphiphilic systems, such as those composed of a hydrophobic polydimethylsiloxane matrix and a hydrophilic polyethyleneglycol additive a...
Article
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Colitis is a common disease of the colon that is very difficult to treat. Probiotic bacteria could be an effective treatment. The probiotic Escherichia coli Nissle 1917 (EcN) was engineered to synthesize the ketone body (R)-3-hydroxybutyrate (3HB) for sustainable production in the gut lumen of mice suffering from colitis. Components of heterologous...
Article
Full-text available
Polyhydroxyalkanoates (PHA) are a promising and sustainable alternative to the petroleum‐based synthetic plastics. Regulation of PHA synthesis is receiving considerable importance as engineering the regulatory factors might help developing strains with improved PHA‐producing abilities. PHA synthesis is dedicatedly regulated by a number of regulator...
Article
Full-text available
d-β-hydroxybutyrate (d-3HB), a monomer of microbial polyhydroxybutyrate (PHB), is also a natural ketone body produced during carbohydrate deprivation to provide energy to the body cells, heart, and brain. In recent years, increasing evidence demonstrates that d-3HB can induce pleiotropic effects on the human body which are highly beneficial for imp...
Article
Waste straw bio-transformation of high value-added macromolecule polyhydroxyalkanoates (PHAs) was significance to environmental sustainable development. As a member of the PHA family, poly-β-hydroxybutyrate (PHB) could be synthesized by Halomonas elongata A1 with maximal yields of 22.8% and 11.8% of bacterial weights using glucose and carboxymethyl...
Article
Full-text available
Bacterial outer membrane (OM), an asymmetric lipid bilayer functioning as a self-protective barrier with reduced permeability for Gram-negative bacteria, yet wasting nutrients and energy to synthesize, has not been studied for its effect on bioproduction. Here we construct several OM-defected halophile Halomonas bluephagenesis strains to investigat...
Article
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Polyhydroxyalkanoate (PHA) is a family of biodegradable polyesters synthesized by microorganisms. It has various monomer structures and physical properties with broad application prospects. However, its large-scale production is still hindered by the high cost. In the past 30 years, metabolic engineering approach has been used to tune the metabolic...
Preprint
Full-text available
This article introduces the EU Horizon 2020 research project MIX-UP, “Mixed plastics biodegradation and upcycling using microbial communities”. The project focuses on the ambitious vision to change the traditional linear value chain of plastics to a sustainable, biodegradable based one. In MIX-UP, plastic mixtures containing five of the top six fos...
Article
Full-text available
Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body...
Article
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With the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and hi...
Article
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The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an unprecedented threat to the human health. A close association of the digestive tract is implied by the high frequency of gastrointestinal syndromes among COVID-19 patients. A better understanding of the role of i...
Article
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3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and contin...
Article
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Genetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bio-processes is still a challenge in metabolic engineering due to the lack of robustness...
Article
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Halomonas bluephagenesis has been successfully engineered to produce multiple products under open unsterile conditions utilizing costly glucose as the carbon source. It would be highly interesting to investigate if H. bluephagenesis, a chassis for the Next Generation Industrial Biotechnology (NGIB), can be reconstructed to become an extracellular h...
Article
Although macroalgae biomass is an emerging sustainable feedstock for biorefineries, the optimum process parameters for their hydrolysis and fermentation are still not known. In the present study, the simultaneous production of polyhydroxyalkanoates (PHA) and biochar from green macroalgae Ulva sp. is examined, applying subcritical water hydrolysis a...
Article
Polyhydroxyalkanoates (PHAs) are a diverse family of sustainable bioplastics synthesized by various bacteria, but their high production cost and unstable material properties make them challenging to use in commercial applications. Current industrial biotechnology (CIB) employs conventional microbial chassis, leading to high production costs. Howeve...
Preprint
Full-text available
Enzymatic reactions in cells are well organized into different compartments, among which protein-based membraneless compartments formed through liquid-liquid phase separation (LLPS) are believed to play important roles. Hijacking them for our own purpose has promising applications in metabolic engineering. Yet, it is still hard to precisely and dyn...
Preprint
Full-text available
Enzymatic reactions in cells are well organized into different compartments, among which protein-based membraneless compartments formed through liquid-liquid phase separation (LLPS) are believed to play important roles 1,2 . Hijacking them for our own purpose has promising applications in metabolic engineering ³ . Yet, it is still hard to precisely...
Article
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Future fermentations will be open, continuous and automatically controlled with fresh water and energy saving. The production strains will be extremophiles engineered by synthetic biology. Microbial fermentations produce chemicals, materials, biofuels, foods and medicines for many years. The processes are less competitive compared to chemical indus...
Article
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Ectoine, a compatible solute synthesized by many halophiles for hypersalinity resistance, has been successfully produced by metabolically engineered Halomonas bluephagenesis, which is a bioplastic poly(3-hydroxybutyrate) producer allowing open unsterile and continuous conditions. Here we report a de novo synthesis pathway for ectoine constructed in...
Article
Aeromonas hydrophila 4AK4 normally produces the copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) using lauric acid as the carbon source. In this study we reported the metabolic engineering of A. hydrophila 4AK4 for the production of polyhydroxyalkanoate (PHA) using acetate as a main carbon source. Recombinant A. hydrophila overexpress...
Article
Polyhydroxyalkanoate (PHA) is a representative biodegradable polymer with more than 150 varieties and various properties. This article reviews the research status and potential applications of PHA, and introduces the properties of four-generation commercial PHA and its research progress in blend fibers with other biodegradable materials.
Article
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Propane and butane are the main constituents of liquefied petroleum gas and are used extensively for transport and domestic use. They are clean burning fuels, suitable for the development of low carbon footprint fuel and energy policies. Here, we present blueprints for the production of bio-alkane gas (propane and butane) through the conversion of...
Article
Halophilic Halomonas bluephagenesis (H. bluephagenesis), a chassis for cost-effective Next Generation Industrial Biotechnology (NGIB), was for the first time engineered to successfully produce L-threonine, one of the aspartic family amino acids (AFAAs). Five exogenous genes including thrA*BC, lysC* and rhtC encoding homoserine dehydrogenase mutant...
Article
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Polyhydroxyalkanoates (PHA) have found widespread medical applications due to their biocompatibility and biodegradability, while further chemical modification requires functional groups on PHA. Halomonas bluephagenesis, a non-model halophilic bacterium serving as a chassis for the Next Generation Industrial Biotechnology (NGIB), was successfully en...
Article
Microbial poly‐3‐hydroxybutyrate (PHB) has been produced via microbial fermentation and safely used as feed additives for sea based large yellow croakers and sensitive land based weaned piglets. PHB maybe also PHA could One day replace petrochemical plastics to save animals that ingest discarded plastics. This is reported by Xuan Wang, Xiao‐Ran Jia...
Article
Chinese biochemical engineering is committed to supporting the chemical and food industries, to advance science and technology frontiers, and to meet major demands of Chinese society and national economic development. This paper reviews the development of biochemical engineering, strategic deployment of these technologies by the government, industr...
Article
Full-text available
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biopolyester with good mechanical properties and biodegradability. Large-scale production of PHBV is still hindered by the high production cost. CRISPR/Cas9 method was used to engineer the TCA cycle in Halomonas bluephagenesis on its chromosome for production of PHBV from glucose as...
Article
Polyhydroxyalkanoates (PHAs) are a diverse family of biopolyesters synthesized by many natural or engineered bacteria. Synthetic biology and DNA-editing approaches have been adopted to engineer cells for more efficient PHA production. Recent advances in synthetic biology applied to improve PHA biosynthesis include ribosome-binding site (RBS) optimi...
Article
Full-text available
Polyhydroxyalkanoates (PHA) have been produced by several bacteria as bioplastics in industrial scales. PHA commercialization has been challenging due to its complexity and the associated high cost together with instabilities on molecular weights (Mw) and structures, thus instability on thermo- and mechanical properties. PHA high production cost is...
Article
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Optimization of intracellular biosynthesis process involving regulation of multiple gene expressions is dependent on the efficient and accurate expression of each expression unit independently. However, challenges of analyzing intermediate products seriously hinder the application of high throughput assays. This study aimed to develop an engineerin...
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Natural organisms have evolved intricate regulatory mechanisms that sense and respond to fluctuating environmental temperatures in a heat-or cold-inducible fashion. Unlike dominant heat-inducible switches, very few cold-inducible genetic switches are available in either natural or engineered systems. Moreover, the available cold-inducible switches...
Article
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PHA, a family of natural biopolymers aiming to replace non-degradable plastics for short-term usages, has been developed to include various structures such as short-chain-length (scl) and medium-chain-length (mcl) monomers as well as their copolymers. However, PHA market has been grown slowly since 1980s due to limited variety with good mechanical...
Article
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The large‐scale use of petrochemical‐based plastics is damaging our environment, Discarded plastics are harmful to both marine and land animals, sometimes causing death when ingested. Biodegradable plastics have gained attentions to reduce environmental burdens. Poly‐3‐hydroxybutrate (PHB), the simplest and the best‐studied bioplastic member of the...
Preprint
Full-text available
Liquefied Petroleum Gas (LPG) is a major domestic and transport fuel. Its combustion lessens NOx, greenhouse gas and particulates emissions compared to other fuels. Propane - the major constituent of LPG - is a clean, high value drop-in fuel that can help governments develop integrated fuels and energy policies with low carbon burden, providing sol...
Article
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Synthetic organogels/hydrogels are attracting growing interests due to their potential applications in biomedical fields, organic electronics and photovoltaics. Photo-gelation methods for synthesis of organogels/hydrogels have shown particularly promising because of the high efficiency and simple synthetic procedures. This study synthesized new bio...
Article
Full-text available
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a promising biopolyester with good mechanical properties and biodegradability. Large-scale production of PHBV is still hindered by the high production cost. CRISPR/Cas9 method was used to engineer the TCA cycle in Halomonas bluephagenesis on its chromosome for production of PHBV from glucose as...