Tao Chen

Tianjin University | tju · School of Chemical Engineering and Technology

Engineering cellular metabolism for improved production of valuable chemicals requires extensive modulation of bacterial genome to explore complex genetic spaces. Here, we report the development of a CRISPR-Cas9 based method for iterative genome editing and metabolic engineering of Escherichia coli. This system enables us to introduce various types...

In this work, modular engineering of Escherichia coli was peformed to improve flavin production and the conversion ratio of riboflavin (RF) to FMN/FAD. The RF operon and the bifunctional RF kinase/FAD synthetase were divided into two separated modules. The two modules were expressed at different levels to produce RF:ribF ratios ranging from 2:20 to...

Background: Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the prod...

Heme, an iron-containing porphyrin derivative, holds great promise in fields like medicine, food production and chemicals. Here, we developed an engineered Corynebacterium glutamicum strain for efficient heme production by combining modular engineering and RBS engineering. The whole heme biosynthetic pathway was methodically divided into 5-ALA synt...

Nicotinamide mononucleotide (NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+), which is widely applied in the pharmaceutical and biotech industries. The biosynthesis of NMN is currently attracting much attention because it has non-toxic reaction conditions and low amounts of isomers, whereas chemical synthesis has low yiel...

Riboswitches are functional RNA elements that regulate gene expression by directly detecting metabolites. Twenty years have passed since it was first discovered, researches on riboswitches are becoming increasingly standardized and refined, which could significantly promote people's cognition of RNA function as well. Here, we focus on some represen...

Acetoin, an important and high-value added bio-based platform chemical, has been widely applied in fields of foods, cosmetics, chemical synthesis, and agriculture. Lactate is a significant intermediate short-chain carboxylate in the anaerobic breakdown of carbohydrates that comprise ~ 18% and ~ 70% in municipal wastewaters and some food processing...

Heme b, which is characterized by a ferrous ion and a porphyrin macrocycle, acts as a prosthetic group for many enzymes and contributes to various physiological processes. Consequently, it has wide applications in medicine, food, chemical production, and other burgeoning fields. Due to the shortcomings of chemical syntheses and bio-extraction techn...

5-Aminolevulinic acid (5-ALA) has recently received much attention for its wide applications in medicine and agriculture. In this study, we investigated the effect of NCgl0580 in Corynebacterium glutamicum on 5-ALA biosynthesis as well as its possible mechanism. It was found that the overexpression of NCgl0580 increased 5-ALA production by approxim...

3-Hydroxypropionic acid (3-HP) is a platform chemical with a wide range of existing and potential applications, including the production of poly(3-hydroxypropionate) (P-3HP), a biodegradable plastic. The microbial synthesis of 3-HP has attracted significant attention in recent years due to its green and sustainable properties. In this paper, we pro...

Shewanella oneidensis is able to carry out extracellular electron transfer (EET), although its EET efficiency is largely limited by low flavin concentrations, poor biofilm forming‐ability, and weak biofilm conductivity. After identifying an important role for riboflavin (RF) in EET via in vitro experiments, the synthesis of RF is directed to 837.74...

Strain engineering for industrial production requires the improvement of tolerance to multiple unfavorable conditions. Here, we report global regulator libraries based on the CRISPR‐enabled trackable genome engineering to engineer tolerance against multiple inhibitors in Escherichia coli. Deep mutagenesis libraries were rationally designed, and con...

Acetoin is an important platform chemical, which has a wide range of applications in many industries. Halomonas bluephagenesis, a chassis for next generation of industrial biotechnology, has advantages of fast growth and high tolerance to organic acid salts and alkaline environment. Here, α-acetolactate synthase and α-acetolactate decarboxylase fro...

A novel xylose regulatory mechanism mediated by the transcription factor IpsA was revealed. A synergistic effect on carbon metabolism and energy supply was found to endow C. glutamicum with the efficient xylose utilization and rapid growth phenotype.

Halomonas spp. are the well-studied platform organisms or chassis for next-generation industrial biotechnology (NGIB) due to their contamination-resistant nature combined with their fast growth property. Several Halomonas spp. have been studied regarding their genomic information and molecular engineering approaches. Halomonas spp., especially Halo...

Microbial fuel cells (MFCs), unique biosystems that generate energy through exoelectrogens, have undergone significant development in the past decades. Although MFCs has great prospects in environmental protection and power generation, there are still problems of inefficiency and high cost, which are largely attributed to the low performance of ano...

5-Aminolevulinic acid (5-ALA), a vital precursor for the biosynthesis of tetrapyrrole compounds, has been widely applied in agriculture and medicine, while extremely potential for the treatment of cancers, corona virus disease 2019 (COVID-19) and metabolic diseases in recent years. With the development of metabolic engineering and synthetic biology...

Background 2,3-butanediol is an important platform compound which has a wide range of applications, involving in medicine, chemical industry, food and other fields. Especially the optically pure (2R,3R)-2,3-butanediol can be employed as an antifreeze agent and as the precursor for producing chiral compounds. However, some (2R,3R)-2,3-butanediol ove...

Acetate is a promising economical and sustainable carbon source for bioproduction, but it is also a known cell-growth inhibitor. In this study, adaptive laboratory evolution (ALE) with acetate as selective pressure was applied to Halomonas bluephagenesis TD1.0, a fast-growing and contamination-resistant halophilic bacterium that naturally accumulat...

Background In vivo biosensors have a wide range of applications, ranging from the detection of metabolites to the regulation of metabolic networks, providing versatile tools for synthetic biology and metabolic engineering. However, in view of the vast array of metabolite molecules, the existing number and performance of biosensors is far from suffi...

Background:2,3-butanediol is an important platform compound which has a wide range of applications, involving in medicine, chemical industry, food and other fields. Especially the optically pure (2R,3R)-2,3-butanediol can be employed as an antifreeze agent and as the precursor for producing chiral compounds. However, some (2R,3R)-2,3-butanediol ove...

5-Aminolevulinic acid (5-ALA) is the key precursor for the biosynthesis of tetrapyrrole compounds, with wide applications in medicine, agriculture and other burgeoning fields. Because of its potential applications and disadvantages of chemical synthesis, alternative biotechnological methods have drawn increasing attention. In this review, the recen...

Acetate is an economical and environmental-friendly alternative carbon source. Herein, the potential of harnessing Corynebacterium glutamicum as a host to produce 3-hydroxypropionic acid (3-HP) from acetate was explored. First, the expression level of malonyl-CoA reductase from Chloroflexus aurantiacus was optimized through several strategies, stra...

Plants produce diverse natural products, and some of them are drugs or drug precursors. Especially, traditional Chinese medical herbs and other medical plants have the capacity to produce a wide range of bioactive compounds. The extraction of these natural products from plants requires substantial time, land and water usage, and they often produce...

Acetoin, a high-value-added bio-based platform chemical, is widely used in foods, cosmetics, agriculture, and the chemical industry. It is an important precursor for the synthesis of: 2,3-butanediol, liquid hydrocarbon fuels and heterocyclic compounds. Since the fossil resources are becoming increasingly scarce, biological production of acetoin has...

As a new interdisciplinary field, synthetic biology has led to valuable innovations in the fields of medicine, chemistry, agriculture, energy and environment. In this paper, we systematically review the development status of global synthetic biology in the past six years, and make an in-depth benchmarking analysis of the field in China. With the ai...

Riboflavin is a commercially important compound in the food, pharmaceutical, chemical, and cosmetic industries. The down-regulation of expression levels of ribF, purA and guaC genes involved in the downstream or branch reactions of riboflavin biosynthesis pathway could direct more carbon flux to riboflavin accumulation. In this study, we made an at...

Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic res...

β-Alanine (3-aminopropionic acid) is the only naturally occurring β-type amino acid. Although it is not incorporated into proteins, it has important physiological functions in the metabolism of animals, plants and microorganisms. Furthermore, it has attracted great interest due to its wide usage as a precursor of many significant industrial chemica...

To explore the suitability of Corynebacterium glutamicum as a chassis for diacetyl production from glucose, diacetyl metabolic pathway and the respiratory chain were linked to achieve redox balance. The carbon flux was redirected from pyruvate to diacetyl by overexpressing the α-acetolactate synthase, in combination with disruption the biosynthetic...

Electroactive microorganisms (EAMs) are ubiquitous in nature and have attracted considerable attention as they can be used for energy recovery and environmental remediation via their extracellular electron transfer (EET) capabilities. Although the EET mechanisms of Shewanella and Geobacter have been rigorously investigated and are well characterize...

In recent years, metabolic engineering has made great progress in both academic research and industrial applications. However, we have not found any articles that specifically analyze the current state of metabolic engineering in China in comparison with other countries. Here, we review the current development and future trends of global metabolic...

Acetoin, especially its enantiomers (3R)- and (3S)-acetoin, is a high-value added bio-based platform chemical with wide applications in the food, cosmetic, agricultural and chemical industries, which consequently gains great attention for its efficient biosynthesis. Recently, cell-free/in vitro biosynthesis has emerged as a promising alternative to...

Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds. Here, the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in Escherichia coli. First, glutamine synthesis was improved b...

Formate can be efficiently produced via electrochemical or photochemical catalytic conversion of CO2, and it can be directly used as an organic carbon source by microorganisms. In theory, formate can be used as the sole carbon source for the microbial production of high-value-added chemicals. Consequently, the construction of efficient formate-assi...

The shikimate pathway is indispensable for the biosynthesis of natural products with aromatic moieties. These products have wide current and potential applications in food, cosmetics and medicine, and consequently have great commercial value. However, compounds extracted from various plants or synthesized from petrochemicals no longer satisfy the r...

Over the past decade, 5-aminolevulinic acid (5-ALA) has been highlighted as a promising functional feed additive and immunomodulator for improving the general health, immune response, and resistance to disease of livestock and poultry. However, it is very costly to produce 5-ALA using conventional chemical synthesis methods. Classical microbial fer...

Beta (β)-carotene (C40H56; a provitamin) is a particularly important carotenoid for human health. Many studies have focused on engineering Escherichia coli as an efficient heterologous producer of β-carotene. Moreover, several strains with potential for use in the industrial production of this provitamin have already been constructed via different...

Strengthening practical teaching, together with improving innovation ability is one of the key tasks of Emerging Engineering Education. This paper is based on the revision of the training program of bioengineering in School of Chemical Engineering and Technology, Tianjin University, improved the practical teaching system and curriculum content, bui...

The growing threat of antimicrobial resistance poses a serious threat to public health care and motivates efforts to understand the means by which resistance acquisition occurs and how this can be combatted. To address these challenges, we expedited the identification of novel mutations that enable complex phenotypic changes that result in improved...

Halomonas TD01, which can grow under non-sterile and continuous processes at high pH and high salt concentrations, is a robust platform for PHA production from glucose. For extending other low-cost sustainable substrates and increasing the potential application in other value-added products, a better understanding of substrates utilization and chem...

Background: Acetoin, especially the optically pure L-(+)- or D-(-)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the pro...

Background: Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the produ...

Riboflavin (RF) and its active forms, the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have been extensively used in the food, feed and pharmaceutical industries. Modern commercial production of riboflavin is based on microbial fermentation, but the established genetically engineered production strains are facing new...

Bioreactors of various forms have been widely used in environmental protection, healthcare, industrial biotechnology, and space exploration. Robust demand in the field stimulated the development of novel designs of bioreactor geometries and process control strategies and the evolution of the physical structure of the control system. After the intro...

1-Deoxynojirimycin (1-DNJ), a polyhydroxylated alkaloid, is a highly selective and potent glycosidase inhibitor that has garnered great interest as a tool to study cellular recognition and as a potential therapeutic agent. The development of analytical methods for the quantification polyhydroxylated alkaloids in natural products requires a multifac...

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...

Background: Metabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in multiplex genome editing technologies. However, simultaneously modulating multiple genes on the chromosome remains challenging in Bacillus subtilis. Thus, developing an effic...

In natural produced bacteria, β-carotene hydroxylase (CrtZ) and β-carotene ketolase (CrtW) convert β-carotene into astaxanthin. To increase astaxanthin production in heterologous strain, simple and effective strategies based on the co-expression of CrtZ and CrtW were applied in E. coli. First, nine artificial operons containing crtZ and crtW genes...

BACKGROUND Acetoin, especially the chiral l‐(+)‐ or d‐(−)‐enantiomer, is a high‐value industrial product that can be used as a pharmaceutical intermediate. However, the production of optically pure acetoin via conventional chemical synthesis is expensive. Classical microbial fermentations satisfy the criteria of green chemistry, but have numerous d...

Lactoyl-CoA is critical for the biosynthesis of biodegradable and biocompatible lactate-based copolymers, which have wide applications. However, reports on acetyl-CoA: lactate CoA-transferases (ALCTs) are rare. To exploit novel ALCTs, amino acid sequence similarity searches based on the CoA-transferases from Clostridium propionicum and Megasphaera...

Anaerobic fermentation is a favorable process for microbial production of bulk chemicals like ethanol and organic acids. Low productivity is the bottleneck of several anaerobic processes which has significant impact on the technique competitiveness of production strain. Improving growth rate of production strain can speed up the total production cy...

Genome editing using engineered nucleases has rapidly transformed from a niche technology to a mainstream method used in various host cells. Its widespread adoption has been largely developed by the emergence of the clustered regularly interspaced short palindromic repeats (CRISPR) system, which uses an easily customizable specificity RNA-guided DN...

Marine ammonia-oxidizing archaea (AOA) play an important role in the global nitrogen cycle by obtaining energy for biomass production from CO2 via oxidation of ammonium. The isolation of Candidatus “Nitrosopumilus maritimus” strain SCM1, which represents the globally distributed AOA in the ocean, provided an opportunity for uncovering the contribut...

Commercial riboflavin production with Bacillus subtilis has been developed by combining rational and classical strain development for almost two decades, but how an improved riboflavin producer can be created rationally is still not completely understood. In this study, we demonstrate the combined use of integrated genomic and transcriptomic analys...

BACKGROUND Acetoin and xylitol are widely used as high‐value platform chemicals with numerous potential applications. Especially the chiral enantiomers L‐(+)‐ and D‐(‐)‐acetoin are used as pharmaceutical intermediates. Cell‐free biosynthesis has many applications in chemicals production, but efficient methods for production of optically pure acetoi...

Objective: To develop an efficient synthetic promoter library for fine-tuned expression of target genes in Corynebacterium glutamicum. Results: A synthetic promoter library for C. glutamicum was developed based on conserved sequences of the - 10 and - 35 regions. The synthetic promoter library covered a wide range of strengths, ranging from 1 to...

Background: Succinate has been recognized as one of the most important bio-based building block chemicals due to its numerous potential applications. However, efficient methods for the production of succinate from lignocellulosic feedstock were rarely reported. Nevertheless, Corynebacterium glutamicum was engineered to efficiently produce succinat...

BACKGROUND Hemicellulose is considered as one of the most abundant renewable bio‐resources and has been utilized as substrate for the manufacture of numerous bio‐products through microbiological approaches. However, it was rarely reported that acetoin was produced directly from hemicellulose by microbial fermentation via consolidated bioprocessing...

Objectives: To investigate the capacity of a genome-reduced Bacillus subtilis strain as chassis cell for acetoin production from xylose. Results: To endow the genome-reduced Bacillus subtilis strain BSK814 with the ability to utilize xylose, we inserted a native xyl operon into its genome and deleted the araR gene. The resulting strain BSK814A2...

Acetoin is a high-value-added industrial product and a promising bio-based platform chemical. The two chiral enantiomers of acetoin are important potential pharmaceutical intermediates. However, at present it is very costly to produce optically pure acetoin using conventional chemical synthesis methods, while classical biocatalysis fulfils many key...

Objective: To construct a strain of Corynebacterium glutamicum capable of efficiently producing 5-aminolevulinic acid (5-ALA) via the C4 pathway by modification of serine and glycine pathway using glucose as sole carbon source. Results: The recombinant C. glutamicum strain AP2 harboring a codon-optimized hemA gene from Rhodobacter sphaeroides wa...

In E. coli, glyA encodes for serine hydroxymethyltransferase (SHMT), which converts L-serine to glycine. When engineering L-serine-producing strains, it is therefore favorable to inactivate glyA to prevent L-serine degradation. However, most glyA knockout strains exhibit slow cell growth because of the resulting lack of glycine and C1 units. To ove...

The introduction of an NADH/NAD+ regeneration system can regulate the distribution between acetoin and 2,3-butanediol. NADH regeneration can also enhance butanol production in coculture fermentation. In this work, a novel artificial consortium of Paenibacillus polymyxa CJX518 and recombinant Escherichia coli LS02T that produces riboflavin (VB2) was...

Design and construction of synthetic microbial consortia is a promising strategy to enhance the performance of bioelectrochemical systems (BESs) and to accelerate practical applications in bioenergy production. According to the design principle of “division-of-labor”, we synthesized a three-species microbial consortium for power generation, consist...

BACKGROUND Poly(3‐hydroxybutyrate) ( PHB ), which is completely biodegradable, is considered a potential candidate to replace a number of petroleum‐derived polymers due to similar mechanical properties. In a previous study, inactivation of ndh gene in E. coli , which encodes the NDH‐II dehydrogenase, resulted in significantly increased PHB producti...

3-Hydroxypropanoic acid (3-HP) is an important biomass-derivable platform chemical that can be converted into a number of industrially relevant compounds. There have been several attempts to produce 3-HP from renewable sources in cell factories, focusing mainly on Escherichia coli, Klebsiella pneumoniae, and Saccharomyces cerevisiae. Despite the si...

Over 100 genome-scale metabolic networks (GSMNs) have been published in recent years and widely used for phenotype prediction and pathway design. However, GSMNs for a specific organism reconstructed by different research groups usually produce inconsistent simulation results, which makes it difficult to use the GSMNs for precise optimal pathway des...

The calculated aerobic growth capabilities of four models using 48 different carbon sources. (XLSX)

The detailed information about reactions corrected when 48 substrates were used as individual carbon sources. (DOCX)

SBML format file for the updated version of iJN746. (XML)

SBML format file for the updated version of PpuMBEL1071. (XML)

Biomass compositions and precursor coefficients in four original models. (XLSX)