1,409 results match your criteria Metabolic Engineering [Journal]


Genome scale metabolic modeling reveals the metabolic potential of three Type II methanotrophs of the genus Methylocystis.

Metab Eng 2019 Apr 15. Epub 2019 Apr 15.

Departamento de Ingeniería Química y Tecnología del medio ambiente, Escuela de Ingenierías Industriales, Universidad de Valladolid, Spain; Institute of Sustainable Processes, Universidad de Valladolid, Spain.

Genome Scale Metabolic Models (GSMMs) of the recently sequenced Methylocystis hirsuta and two other methanotrophs from the genus Methylocystis have been reconstructed. These organisms are Type II methanotrophs with the ability of accumulating Polyhydroxyalkanoates under nutrient limiting conditions. For the first time, GSMMs have been reconstructed for Type II methanotrophs. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.04.001DOI Listing

Expanded synthetic small regulatory RNA expression platforms for rapid and multiplex gene expression knockdown.

Metab Eng 2019 Apr 15. Epub 2019 Apr 15.

Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea; Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST, Daejeon 34141, Republic of Korea; BioProcess Engineering Research Center and BioInformatics Research Center, KAIST, 34141 Daejeon, Republic of Korea. Electronic address:

Synthetic small regulatory RNA (sRNA) can efficiently downregulate target gene expression at translational level in metabolic engineering, but cannot be used in engineered strain already having incompatible plasmid(s). To address this problem and make the sRNA gene expression modulation platform universally applicable, we report the development and applications of expanded synthetic sRNA expression platforms for rapid, multiplexed and genome-scale target gene knockdown in engineered Escherichia coli. As proof-of-concept, high performance strains capable of producing L-proline (54. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.04.003DOI Listing

Metabolic engineering of the type I methanotroph Methylomonas sp. DH-1 for production of succinate from methane.

Metab Eng 2019 Apr 12;54:170-179. Epub 2019 Apr 12.

Department of Chemical Engineering, Kyung Hee University, Gyeonggi-do 17104, Republic of Korea. Electronic address:

Methane-utilizing methanotrophs are fascinating systems for methane bioconversion. Methylomonas sp. DH-1, a novel type I methanotroph isolated from brewery sludge, has been evaluated as a promising candidate for an industrial bio-catalyst. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.013DOI Listing

Engineering Lactococcus lactis for the production of unusual anthocyanins using tea as substrate.

Metab Eng 2019 Apr 10;54:160-169. Epub 2019 Apr 10.

Molecular Genetics, University of Groningen, Groningen, Netherlands. Electronic address:

Plant material rich in anthocyanins has been historically used in traditional medicines, but only recently have the specific pharmacological properties of these compounds been the target of extensive studies. In addition to their potential to modulate the development of various diseases, coloured anthocyanins are valuable natural alternatives commonly used to replace synthetic colourants in food industry. Exploitation of microbial hosts as cell factories is an attractive alternative to extraction of anthocyanins and other flavonoids from plant sources or chemical synthesis. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.04.002DOI Listing
April 2019
1 Read

Manipulation of polyhydroxyalkanoate granular sizes in Halomonas bluephagenesis.

Metab Eng 2019 Apr 6;54:117-126. Epub 2019 Apr 6.

MOE Key Lab of Bioinformatics, School of Life Science, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China; MOE Key Lab of Industrial Biocatalysis, Dept of Chemical Engineering, Tsinghua University, Beijing, 100084, China. Electronic address:

Bacterial polyhydroxyalkanoates (PHA) are a family of intracellular polyester granules with sizes ranging from 100 to 500 nm. Due to their small sizes, it has been very difficult to separate the PHA granules from the bacterial broths. This study aims to engineer the PHA size control mechanism to obtain large PHA granular sizes beneficial for the separation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176193009
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http://dx.doi.org/10.1016/j.ymben.2019.03.011DOI Listing
April 2019
2 Reads

Kick-starting evolution efficiency with an autonomous evolution mutation system.

Metab Eng 2019 Apr 3;54:127-136. Epub 2019 Apr 3.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China; Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, China. Electronic address:

Adaptive evolution is an effective strategy to obtain industrial strains with excellent performance, but this method is time-consuming and less efficient. To solve these problems, we constructed an autonomous evolution mutation system (AEMS) to promote the occurrence of mutations, based on the hierarchical dynamic control between the high-fidelity module and the mutagenic module. AEMS was applied in Bacillus subtilis to screen acetoin tolerance phenotypes and high-producing strains. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.010DOI Listing

Multi-level engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalysts for the production of C9 chemicals from oleic acid.

Metab Eng 2019 Apr 4;54:137-144. Epub 2019 Apr 4.

Department of Food Science & Engineering, Ewha Womans University, Seoul, 03760, Republic of Korea. Electronic address:

Whole-cell biotransformation is one of the promising alternative approaches to microbial fermentation for producing high-value chemicals. Baeyer-Villiger monooxygenase (BVMO)-based Escherichia coli biocatalysts have been engineered to produce industrially relevant C9 chemicals, such as n-nonanoic acid and 9-hydroxynonanoic acid, from a renewable long-chain fatty acid. The key enzyme in the biotransformation pathway (i. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.012DOI Listing
April 2019
1 Read

Coupling feedback genetic circuits with growth phenotype for dynamic population control and intelligent bioproduction.

Metab Eng 2019 Mar 30;54:109-116. Epub 2019 Mar 30.

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA. Electronic address:

Metabolic engineering entails target modification of cell metabolism to maximize cell's production potential. Due to the complexity of cell metabolism, feedback genetic circuits have emerged as basic tools to combat metabolic heterogeneity, enhance microbial cooperation as well as boost cell's productivity. This is generally achieved by applying social reward-punishment rules to eliminate cheaters and reward winners in a mixed cell population. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.009DOI Listing
March 2019
2 Reads

Metabolic engineering advances and prospects for amino acid production.

Metab Eng 2019 Mar 30. Epub 2019 Mar 30.

Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany. Electronic address:

Amino acid fermentation is one of the major pillars of industrial biotechnology. The multi-billion USD amino acid market is rising steadily and is diversifying. Metabolic engineering is no longer focused solely on strain development for the bulk amino acids L-glutamate and L-lysine that are produced at the million-ton scale, but targets specialty amino acids. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176193010
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http://dx.doi.org/10.1016/j.ymben.2019.03.008DOI Listing
March 2019
7 Reads
6.767 Impact Factor

From nutritional wealth to autophagy: In vivo metabolic dynamics in the cytosol, mitochondrion and shuttles of IgG producing CHO cells.

Metab Eng 2019 Mar 28;54:145-159. Epub 2019 Mar 28.

Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. Electronic address:

To fulfil the optimization needs of current biopharmaceutical processes the knowledge how to improve cell specific productivities is of outmost importance. This requires a detailed understanding of cellular metabolism on a subcellular level inside compartments such as cytosol and mitochondrion. Using IgG1 producing Chinese hamster ovary (CHO) cells, a pioneering protocol for compartment-specific metabolome analysis was applied. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.02.005DOI Listing

Chromosome engineering of the TCA cycle in Halomonas bluephagenesis for production of copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV).

Metab Eng 2019 Mar 23;54:69-82. Epub 2019 Mar 23.

MOE Key Lab for Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China; MOE Key Lab for Industrial Biocatalysis, Dept Chemical Engineering, Tsinghua University, Beijing 100084, China; Center for Nano- and Micro-Mechanics, Tsinghua University, Beijing 100084, China. Electronic address:

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 a sole carbon source. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.006DOI Listing

Metabolic engineering for the production of dicarboxylic acids and diamines.

Metab Eng 2019 Mar 21. Epub 2019 Mar 21.

Metabolic and Biomolecular Engineering National Research Laboratory, Systems Metabolic Engineering and Systems Healthcare (SMESH) Cross-Generation Collaborative Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea; Bioinformatics Research Center, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea; BioProcess Engineering Research Center, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. Electronic address:

Microbial production of chemicals and materials from renewable carbon sources is becoming increasingly important to help establish sustainable chemical industry. In this paper, we review current status of metabolic engineering for the bio-based production of linear and saturated dicarboxylic acids and diamines, important platform chemicals used in various industrial applications, especially as monomers for polymer synthesis. Strategies for the bio-based production of various dicarboxylic acids having different carbon numbers including malonic acid (C3), succinic acid (C4), glutaric acid (C5), adipic acid (C6), pimelic acid (C7), suberic acid (C8), azelaic acid (C9), sebacic acid (C10), undecanedioic acid (C11), dodecanedioic acid (C12), brassylic acid (C13), tetradecanedioic acid (C14), and pentadecanedioic acid (C15) are reviewed. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.005DOI Listing

Knockdown of carbonate anhydrase elevates Nannochloropsis productivity at high CO level.

Metab Eng 2019 Mar 20;54:96-108. Epub 2019 Mar 20.

Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China; University of Chinese Academy of Science, Beijing, China. Electronic address:

Improving acid tolerance is pivotal to the development of microalgal feedstock for converting flue gas to biomass or oils. In the industrial oleaginous microalga Nannochloropsis oceanica, transcript knockdown of a cytosolic carbonic anhydrase (CA2), which is a key Carbon Concentrating Mechanism (CCM) component induced under 100 ppm CO (very low carbon, or VLC), results in ∼45%, ∼30% and ∼40% elevation of photosynthetic oxygen evolution rate, growth rate and biomass accumulation rate respectively under 5% CO (high carbon, or HC), as compared to the wild type. Such high-CO-level activated biomass over-production is reproducible across photobioreactor types and cultivation scales. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183044
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http://dx.doi.org/10.1016/j.ymben.2019.03.004DOI Listing
March 2019
14 Reads
6.767 Impact Factor

Exceptional solvent tolerance in Yarrowia lipolytica is enhanced by sterols.

Metab Eng 2019 Mar 15;54:83-95. Epub 2019 Mar 15.

Department of Chemical and Biomolecular Engineering, University of Tennessee, TN 37996, USA. Electronic address:

Green organic solvents such as ionic liquids (ILs) have versatile use but are inhibitory to microbes even at low concentrations of 0.5-1.0% (v/v) ILs. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.003DOI Listing

Metabolic engineering of Chinese hamster ovary cells towards reduced biosynthesis and accumulation of novel growth inhibitors in fed-batch cultures.

Metab Eng 2019 Mar 6;54:54-68. Epub 2019 Mar 6.

Cell Culture Process Development, Pfizer Inc, One Burtt Road, Andover, MA 01810, USA.

Chinese hamster ovary (CHO) cells in fed-batch cultures are known to consume large amounts of nutrients and divert significant portion of them towards the formation of byproducts, some of which, including lactate and ammonia, are known to be growth inhibitory in nature. A major fraction of these inhibitory metabolites are byproducts or intermediates of amino acid catabolism. Limiting the supply of amino acids has been shown to curtail the production of corresponding inhibitory byproducts resulting in enhanced growth and productivities in CHO cell fed-batch cultures (Mulukutla et al. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.001DOI Listing

Balancing the non-linear rosmarinic acid biosynthetic pathway by modular co-culture engineering.

Metab Eng 2019 Mar 5;54:1-11. Epub 2019 Mar 5.

Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Rd, Piscataway, NJ 08854, USA. Electronic address:

Pathway balancing is a critical and common challenge for microbial biosynthesis using metabolic engineering approaches. Non-linear biosynthetic pathways, such as diverging and converging pathways, are particularly difficult for bioproduction optimization, because they require delicate balancing between all interconnected constituent pathway modules. The emergence of modular co-culture engineering offers a new perspective for biosynthetic pathways modularization and balancing, as the biosynthetic capabilities of individual pathway modules can be coordinated by flexible adjustment of the subpopulation ratio of the co-culture strains carrying the designated modules. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.03.002DOI Listing
March 2019
1 Read

De novo production of benzyl glucosinolate in Escherichia coli.

Metab Eng 2019 Mar 1;54:24-34. Epub 2019 Mar 1.

DynaMo Center, Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark. Electronic address:

Microbial production of plant specialised metabolites is challenging as the biosynthetic pathways are often complex and can contain enzymes, which function is not supported in traditional production hosts. Glucosinolates are specialised metabolites of strong commercial interest due to their health-promoting effects. In this work, we engineered the production of benzyl glucosinolate in Escherichia coli. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.02.004DOI Listing

GC-MS-based C metabolic flux analysis resolves the parallel and cyclic glucose metabolism of Pseudomonas putida KT2440 and Pseudomonas aeruginosa PAO1.

Metab Eng 2019 Mar 1;54:35-53. Epub 2019 Mar 1.

Institute of Systems Biotechnology, Saarland University, Campus A 1.5, 66123 Saarbrücken, Germany. Electronic address:

The genus Pseudomonas comprises approximately 200 species with numerous isolates that are common inhabitants of soil, water, and vegetation and has been of particular interest for more than one hundred years. Here, we present a novel approach for accurate, precise and convenient C metabolic flux analysis of these and other microbes possessing periplasmic glucose oxidation and a cyclic hexose metabolism, which forms the recently discovered EDEMP cycle. This complex cyclic architecture cannot be resolved by common metabolic flux workflows, which rely on GC-MS-based labelling analysis of proteinogenic amino acids. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183047
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http://dx.doi.org/10.1016/j.ymben.2019.01.008DOI Listing
March 2019
5 Reads

Substrate promiscuity of enzymes from the sesquiterpene biosynthetic pathways from Artemisia annua and Tanacetum parthenium allows for novel combinatorial sesquiterpene production.

Metab Eng 2019 Feb 26;54:12-23. Epub 2019 Feb 26.

Laboratory of Plant Physiology, Wageningen University and Research, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands. Electronic address:

The therapeutic properties of complex terpenes often depend on the stereochemistry of their functional groups. However, stereospecific chemical synthesis of terpenes is challenging. To overcome this challenge, metabolic engineering can be employed using enzymes with suitable stereospecific catalytic activity. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.01.007DOI Listing
February 2019

Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control.

Metab Eng 2019 05 16;53:35-47. Epub 2019 Feb 16.

Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea; Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea. Electronic address:

Reprogramming of 'adult' differentiated somatic cells to 'embryonic' pluripotent stem cells accompanied by increased rate of glycolysis. Conversely, glycolysis triggers accumulation of advanced glycation end products (AGEs), a potential causative factor in aging, by promoting methylglyoxal production. Therefore, it is reasonable that pluripotent stem cells (PSCs) would specifically regulate glycolysis to maintain their embryonic features. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.02.003DOI Listing
May 2019
1 Read

Glyco-recoded Escherichia coli: Recombineering-based genome editing of native polysaccharide biosynthesis gene clusters.

Metab Eng 2019 05 14;53:59-68. Epub 2019 Feb 14.

Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA; Department of Microbiology, Cornell University, Ithaca, NY 14853, USA. Electronic address:

Recombineering-based redesign of bacterial genomes by adding, removing or editing large segments of genomic DNA is emerging as a powerful technique for expanding the range of functions that an organism can perform. Here, we describe a glyco-recoding strategy whereby major non-essential polysaccharide gene clusters in K-12 Escherichia coli are replaced with orthogonal glycosylation components for both biosynthesis of heterologous glycan structures and site-specific glycan conjugation to target proteins. Specifically, the native enterobacterial common antigen (ECA) and O-polysaccharide (O-PS) antigen loci were systematically replaced with ∼9-10 kbp of synthetic DNA encoding Campylobacter jejuni enzymes required for asparagine-linked (N-linked) protein glycosylation. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.02.002DOI Listing
May 2019
3 Reads

Development of 3-hydroxypropionic-acid-tolerant strain of Escherichia coli W and role of minor global regulator yieP.

Metab Eng 2019 05 7;53:48-58. Epub 2019 Feb 7.

School of Energy and Chemical Engineering, UNIST, Ulsan 44919, Republic of Korea; School of Chemical and Biomolecular Engineering, Pusan National University, Busan 46241, Republic of Korea. Electronic address:

3-Hydroxypropionic acid (3-HP) is an important platform chemical, but its toxic effect at high concentrations (> 200 mM) is a serious challenge for commercial production. In this study, a highly 3-HP-tolerant strain of Escherichia coli W (tolerance concentration: 400 mM in M9 minimal medium and 800 mM when yeast extract was added) was developed by adaptive laboratory evolution (ALE) with glycerol as the carbon source. Genome analysis of the adapted strain (designated as E. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.02.001DOI Listing
May 2019
1 Read

Construction of artificial micro-aerobic metabolism for energy- and carbon-efficient synthesis of medium chain fatty acids in Escherichia coli.

Metab Eng 2019 05 24;53:1-13. Epub 2019 Jan 24.

College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China. Electronic address:

Medium-chain (C-C) chemicals are important components of fuels, commodities and fine chemicals. Numerous exciting achievements have proven reversed β-oxidation cycle as a promising platform to synthesize these chemicals. However, under native central carbon metabolism, energetic and redox constraints limit the efficient operation of reversed β-oxidation cycle. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.01.006DOI Listing
May 2019
7 Reads
6.767 Impact Factor

Systems-level engineering and characterisation of Clostridium autoethanogenum through heterologous production of poly-3-hydroxybutyrate (PHB).

Metab Eng 2019 05 11;53:14-23. Epub 2019 Jan 11.

Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; Metabolomics Australia, AIBN, The University of Queensland, Brisbane, Australia. Electronic address:

Gas fermentation is emerging as an economically attractive option for the sustainable production of fuels and chemicals from gaseous waste feedstocks. Clostridium autoethanogenum can use CO and/or CO + H as its sole carbon and energy sources. Fermentation of C. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.01.003DOI Listing
May 2019
2 Reads

Transomics data-driven, ensemble kinetic modeling for system-level understanding and engineering of the cyanobacteria central metabolism.

Metab Eng 2019 03 8;52:273-283. Epub 2019 Jan 8.

Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:

In silico kinetic modeling is an essential tool for rationally designing metabolically engineered organisms based on a system-level understanding of their regulatory mechanisms. However, an estimation of enzyme parameters has been a bottleneck in the computer simulation of metabolic dynamics. In this study, the ensemble-modeling approach was integrated with the transomics data to construct kinetic models. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183029
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http://dx.doi.org/10.1016/j.ymben.2019.01.004DOI Listing
March 2019
15 Reads

Phage serine integrase-mediated genome engineering for efficient expression of chemical biosynthetic pathway in gas-fermenting Clostridium ljungdahlii.

Metab Eng 2019 03 8;52:293-302. Epub 2019 Jan 8.

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

The real value of gas-fermenting clostridia, capable of using CO and CO, resides in their potential of being developed into cell factories to produce various bulk chemicals and fuels. This process requires rapid chromosomal integration of heterologous chemical biosynthetic pathways, which is impeded by the absence of genetic tools competent for efficient genome engineering in these anaerobes. Here, we developed a phage serine integrase-mediated site-specific genome engineering technique in Clostridium ljungdahlii, one of the major acetogenic gas-fermenting microbes. Read More

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http://dx.doi.org/10.1016/j.ymben.2019.01.005DOI Listing
March 2019
1 Read

Continuous translation of circularized mRNA improves recombinant protein titer.

Metab Eng 2019 03 4;52:284-292. Epub 2019 Jan 4.

National Institute for Cellular Biotechnology, Dublin City University, Dublin D09 NR58, Ireland. Electronic address:

Recent success in demonstrating the translation of circular RNA open reading frames or circular mRNA, may offer a new avenue for improving recombinant protein production from cell and cell-free expression platforms. Initiation and termination are two rate limiting steps of translation. Circular RNA as a class of RNA is defined by covalent joining of terminal ends to give a closed loop structure. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183034
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http://dx.doi.org/10.1016/j.ymben.2019.01.002DOI Listing
March 2019
3 Reads

Pyruvate kinase L/R is a regulator of lipid metabolism and mitochondrial function.

Metab Eng 2019 03 4;52:263-272. Epub 2019 Jan 4.

Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Centre for Host-Microbiome Interactions, Dental Institute, King's College London, London SE1 9RT, United Kingdom. Electronic address:

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) has been associated with altered expression of liver-specific genes including pyruvate kinase liver and red blood cell (PKLR), patatin-like phospholipase domain containing 3 (PNPLA3) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Here, we inhibited and overexpressed the expression of these three genes in HepG2 cells, generated RNA-seq data before and after perturbation and revealed the altered global biological functions with the modulation of these genes using integrated network (IN) analysis. We found that modulation of these genes effects the total triglycerides levels within the cells and viability of the cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183031
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http://dx.doi.org/10.1016/j.ymben.2019.01.001DOI Listing
March 2019
10 Reads

Engineered sigma factors increase full-length antibody expression in Escherichia coli.

Metab Eng 2019 03 2;52:315-323. Epub 2019 Jan 2.

Cell Culture, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address:

Escherichia coli (E. coli) is a promising platform for expression of full-length antibodies owing to its several advantages as a production host (fast growth, well characterized genetics, low manufacturing cost), however, low titers from shake flask (typically < 5 mg/L) has limited its use for production of research-grade material in antibody discovery programs. In this work, we used global transcriptional machinery engineering (gTME) with high throughput screening to increase the expression of full-length antibodies in E. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.009DOI Listing

Engineering microbial membranes to increase stress tolerance of industrial strains.

Metab Eng 2019 05 31;53:24-34. Epub 2018 Dec 31.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China. Electronic address:

The microbial membrane serves as a biological barrier that separates the interior of cells from the external environment, thus playing an important role in tolerance to stress conditions during industrial bioprocessing. Accordingly, engineering or regulation of membrane functions provides a great opportunity to improve the robustness of industrial strains and may enable increased titers, yield, and production of the targeted metabolites. In this review, we summarize the recent progress in metabolic engineering strategies to enhance membrane integrity, regulate membrane fluidity, and tune membrane permeability. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.010DOI Listing

OptSSeq explores enzyme expression and function landscapes to maximize isobutanol production rate.

Metab Eng 2019 03 27;52:324-340. Epub 2018 Dec 27.

DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53726, United States; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, United States. Electronic address:

Efficient microbial production of the next-generation biofuel isobutanol (IBA) is limited by metabolic bottlenecks. Overcoming these bottlenecks will be aided by knowing the optimal ratio of enzymes for efficient flux through the IBA biosynthetic pathway. OptSSeq (Optimization by Selection and Sequencing) accomplishes this goal by tracking growth rate-linked selection of optimal expression elements from a combinatorial library. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.008DOI Listing
March 2019
2 Reads

Engineering Pseudomonas entomophila for synthesis of copolymers with defined fractions of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates.

Metab Eng 2019 03 21;52:253-262. Epub 2018 Dec 21.

Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China; Center for Nano- and Micro-Mechanics, Tsinghua University, Beijing 100084, China. Electronic address:

Polyhydroxyalkanoates (PHA) composed of both short-chain-length (SCL) and medium-chain-length (MCL) monomers (SCL-co-MCL PHA) combine the advantages of high strength and elasticity provided by SCL PHA and MCL PHA, respectively. Synthesis of SCL-co-MCL PHA, namely, copolymers of 3-hydroxybutyrate (3HB) and MCL 3-hydroxyalkanoates (3HA) such as 3-hydroxydecanoate (3HD) and longer chain 3HA, has been a challenge for a long time. This study aims to engineer Pseudomonas entomophila for synthesizing P(3HB-co-MCL 3HA) via weakening its β-oxidation pathway combined with insertion of 3HB synthesis pathway consisting of β-ketothiolase (phaA) and acetoacetyl-CoA reductase (phaB). Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.007DOI Listing
March 2019
6.767 Impact Factor

Construction of a fusion enzyme for astaxanthin formation and its characterisation in microbial and plant hosts: A new tool for engineering ketocarotenoids.

Metab Eng 2019 03 20;52:243-252. Epub 2018 Dec 20.

School of Biological Sciences, Royal Holloway University of London, Egham hill, Egham TW200EX, United Kingdom. Electronic address:

The high-value ketocarotenoid astaxanthin, a natural red colorant with powerful antioxidant activity, is synthesised from β-carotene by a hydroxylase and an oxygenase enzyme, which perform the addition of two hydroxyl and keto moieties, respectively. Several routes of intermediates, depending on the sequence of action of these enzymes, lead to the formation of astaxanthin. In the present study, the enzyme activities of 3, 3' β-carotene hydroxylase (CRTZ) and 4, 4' β-carotene oxygenase (CRTW) have been combined through the creation of "new to nature" enzyme fusions in order to overcome leakage of non-endogenous intermediates and pleotropic effects associated with their high levels in plants. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374281PMC

Engineering two species of yeast as cell factories for 2'-fucosyllactose.

Metab Eng 2019 03 14;52:232-242. Epub 2018 Dec 14.

E.I. du Pont de Nemours and Company (DuPont), Central Research and Development, Experimental Station, Wilmington, DE 19803, USA; E.I. du Pont de Nemours and Company (DuPont), Industrial Biosciences, Experimental Station, Wilmington, DE 19803, USA.

Oligosaccharides present in human breast milk have been linked to beneficial effects on infant health. Inclusion of these human milk oligosaccharides (HMOs) in infant formula can recapitulate these health benefits. As a result, there is substantial commercial interest in a cost-effective source of HMOs as infant formula ingredients. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.005DOI Listing
March 2019
23 Reads

Engineering of the citrate exporter protein enables high citric acid production in Aspergillus niger.

Metab Eng 2019 03 13;52:224-231. Epub 2018 Dec 13.

Austrian Centre of Industrial Biotechnology (ACIB GmbH), Muthgasse 18, Vienna, Austria; Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; CD Laboratory for Biotechnology of Glycerol, Muthgasse 18, Vienna, Austria. Electronic address:

Aspergillus niger was engineered using a gene responsible for citric acid transport, which has a significant impact on citric acid secretion when overexpressed. The transport gene was identified by a homology search using an itaconic acid transporter from Ustilago maydis as template. The encoding homologous protein CexA belongs to the major facilitator superfamily subclass DHA1 and members of this family work as drug-H antiporter. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183037
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http://dx.doi.org/10.1016/j.ymben.2018.12.004DOI Listing
March 2019
3 Reads

Mapping Salmonella typhimurium pathways using C metabolic flux analysis.

Metab Eng 2019 03 4;52:303-314. Epub 2018 Dec 4.

CEB-Centre of Biological Engineering, University of Minho, Campus De Gualtar, Braga 4710-057, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB-NOVA), Oeiras, Portugal. Electronic address:

In the last years, Salmonella has been extensively studied not only due to its importance as a pathogen, but also as a host to produce pharmaceutical compounds. However, the full exploitation of Salmonella as a platform for bioproduct delivery has been hampered by the lack of information about its metabolism. Genome-scale metabolic models can be valuable tools to delineate metabolic engineering strategies as long as they closely represent the actual metabolism of the target organism. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.011DOI Listing

aMSGE: advanced multiplex site-specific genome engineering with orthogonal modular recombinases in actinomycetes.

Metab Eng 2019 03 5;52:153-167. Epub 2018 Dec 5.

College of Life Sciences, Shanghai Normal University, Shanghai 200232, China. Electronic address:

Chromosomal integration of genes and pathways is of particular importance for large-scale and long-term fermentation in industrial biotechnology. However, stable, multi-copy integration of long DNA segments (e.g. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.001DOI Listing
March 2019
2 Reads
6.767 Impact Factor

Deletion of four genes in Escherichia coli enables preferential consumption of xylose and secretion of glucose.

Metab Eng 2019 03 7;52:168-177. Epub 2018 Dec 7.

Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, DE 19716, USA. Electronic address:

Overcoming carbon catabolite repression presents a significant challenge, largely due to the complex regulatory networks governing substrate catabolism, even in microbial cells. In this work, we have engineered an E. coli strain, which we have named X2G, that not only exhibits a reversed substrate preference for xylose over glucose, but also demonstrates an unusual ability to produce significant amounts of glucose. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.003DOI Listing

Magnesium starvation improves production of malonyl-CoA-derived metabolites in Escherichia coli.

Metab Eng 2019 03 6;52:215-223. Epub 2018 Dec 6.

Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:

Starvation of essential nutrients, such as nitrogen, sulfur, magnesium, and phosphorus, leads cells into stationary phase and potentially enhances target metabolite production because cells do not consume carbon for the biomass synthesis. The overall metabolic behavior changes depend on the type of nutrient starvation in Escherichia coli. In the present study, we determined the optimum nutrient starvation type for producing malonyl-CoA-derived metabolites such as 3-hydroxypropionic acid (3HP) and naringenin in E. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.12.002DOI Listing

Stepwise pathway engineering to the biosynthesis of zeaxanthin, astaxanthin and capsanthin in rice endosperm.

Metab Eng 2019 03 29;52:178-189. Epub 2018 Nov 29.

Graduate School of International Agricultural Technology and Crop Biotechnology Institute/GreenBio Science and Technology, Seoul National University, Pyeongchang 25354, Republic of Korea.

Carotenoid pigments are valuable components of the human diet. A notable example is β-carotene, or provitamin A, which is converted into the derivatives astaxanthin and capsanthin, via the common intermediate zeaxanthin. To generate rice varieties producing diverse carotenoids beyond β-carotene, we specifically used a Capsicum β-carotene hydroxylase gene, B (CaBch) and a codon optimized version of the same gene, stB (stBch) to increase zeaxanthin synthesis. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.012DOI Listing
March 2019
28 Reads

Glyco-engineered CHO cell lines producing alpha-1-antitrypsin and C1 esterase inhibitor with fully humanized N-glycosylation profiles.

Metab Eng 2019 03 1;52:143-152. Epub 2018 Dec 1.

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark. Electronic address:

Recombinant Chinese hamster ovary (CHO) cells are able to provide biopharmaceuticals that are essentially free of human viruses and have N-glycosylation profiles similar, but not identical, to humans. Due to differences in N-glycan moieties, two members of the serpin superfamily, alpha-1-antitrypsin (A1AT) and plasma protease C1 inhibitor (C1INH), are currently derived from human plasma for treating A1AT and C1INH deficiency. Deriving therapeutic proteins from human plasma is generally a cost-intensive process and also harbors a risk of transmitting infectious particles. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.014DOI Listing
March 2019
8 Reads

Regulatory non-coding sRNAs in bacterial metabolic pathway engineering.

Metab Eng 2019 03 1;52:190-214. Epub 2018 Dec 1.

McKetta Department of Chemical Engineering, University of Texas at Austin, 200 E. Dean Keeton Street Stop C0400, Austin, TX 78712, USA. Electronic address:

Non-coding RNAs (ncRNAs) are versatile and powerful controllers of gene expression that have been increasingly linked to cellular metabolism and phenotype. In bacteria, identified and characterized ncRNAs range from trans-acting, multi-target small non-coding RNAs to dynamic, cis-encoded regulatory untranslated regions and riboswitches. These native regulators have inspired the design and construction of many synthetic RNA devices. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183020
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http://dx.doi.org/10.1016/j.ymben.2018.11.013DOI Listing
March 2019
10 Reads

Production of plant-specific flavones baicalein and scutellarein in an engineered E. coli from available phenylalanine and tyrosine.

Metab Eng 2019 03 26;52:124-133. Epub 2018 Nov 26.

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

Baicalein and scutellarein are bioactive flavones found in the medicinal plant Scutellaria baicalensis Georgi, used in traditional Chinese medicine. Extensive previous work has demonstrated the broad biological activity of these flavonoids, such as antifibrotic, antiviral and anticancer properties. However, their supply from plant material is insufficient to meet demand. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.008DOI Listing
March 2019
2 Reads

Lipid engineering combined with systematic metabolic engineering of Saccharomyces cerevisiae for high-yield production of lycopene.

Metab Eng 2019 03 22;52:134-142. Epub 2018 Nov 22.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430072, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan 430075, China. Electronic address:

Saccharomyces cerevisiae is an efficient host for natural-compound production and preferentially employed in academic studies and bioindustries. However, S. cerevisiae exhibits limited production capacity for lipophilic natural products, especially compounds that accumulate intracellularly, such as polyketides and carotenoids, with some engineered compounds displaying cytotoxicity. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.009DOI Listing
March 2019
23 Reads

Yeast chemogenomic screen identifies distinct metabolic pathways required to tolerate exposure to phenolic fermentation inhibitors ferulic acid, 4-hydroxybenzoic acid and coniferyl aldehyde.

Metab Eng 2019 03 22;52:98-109. Epub 2018 Nov 22.

Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. Electronic address:

The conversion of plant material into biofuels and high value products is a two-step process of hydrolysing plant lignocellulose and next fermenting the sugars produced. However, lignocellulosic hydrolysis not only frees sugars for fermentation it simultaneously generates toxic chemicals, including phenolic compounds which severely inhibit yeast fermentation. To understand the molecular basis of phenolic compound toxicity, we performed genome-wide chemogenomic screens in Saccharomyces cerevisiae to identify deletion mutants that were either hypersensitive or resistant to three common phenolic compounds found in plant hydrolysates: coniferyl aldehyde, ferulic acid and 4-hydroxybenzoic acid. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183032
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http://dx.doi.org/10.1016/j.ymben.2018.11.010DOI Listing
March 2019
22 Reads

Purity by design: Reducing impurities in bioproduction by stimulus-controlled global translational downregulation of non-product proteins.

Metab Eng 2019 03 20;52:110-123. Epub 2018 Nov 20.

ETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, 4058 Basel, Switzerland; Faculty of Life Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland. Electronic address:

Capitalizing on the ability of mammalian cells to conduct complex post-translational modifications, most protein therapeutics are currently produced in cell culture systems. Addition of a signal peptide to the product protein enables its accumulation in the cell culture supernatant, but separation of the product from endogenously secreted proteins remains costly and labor-intensive. We considered that global downregulation of translation of non-product proteins would be an efficient strategy to minimize downstream processing requirements. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.11.007DOI Listing
March 2019
40 Reads

Editorial Introduction.

Authors:
Hal Alper

Metab Eng 2018 11;50

McKetta Department of Chemical Engineering The University of Texas at Austin 200 E Dean Keeton St. Stop C0400 Austin, TX 78712; Institute for Cellular and Molecular Biology The University of Texas at Austin 2500 Speedway Avenue Austin, Texas 78712. Electronic address:

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http://dx.doi.org/10.1016/j.ymben.2018.11.005DOI Listing
November 2018
12 Reads

Efficient mining of natural NADH-utilizing dehydrogenases enables systematic cofactor engineering of lysine synthesis pathway of Corynebacterium glutamicum.

Metab Eng 2019 03 17;52:77-86. Epub 2018 Nov 17.

Key Laboratory of Industrial Biocatalysis (Ministry of Education), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China; Tsinghua Innovation Center in Dongguan, Dongguan 523808, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China. Electronic address:

Increasing the availability of NADPH is commonly used to improve lysine production by Corynebacterium glutamicum since 4 mol of NADPH are required for the synthesis of 1 mol of lysine. Alternatively, engineering of enzymes in lysine synthesis pathway to utilize NADH directly can also be explored for cofactor balance during lysine overproduction. To achieve such a goal, enzyme mining was used in this study to quickly identify a full set of NADH-utilizing dehydrogenases, namely aspartate dehydrogenase from Pseudomonas aeruginosa (PaASPDH), aspartate-semialdehyde dehydrogenase from Tistrella mobilis (TmASADH), dihydrodipicolinate reductase from Escherichia coli (EcDHDPR), and diaminopimelate dehydrogenase from Pseudothermotoga thermarum (PtDAPDH). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183034
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http://dx.doi.org/10.1016/j.ymben.2018.11.006DOI Listing
March 2019
4 Reads

Kinetic models of metabolism that consider alternative steady-state solutions of intracellular fluxes and concentrations.

Metab Eng 2019 03 26;52:29-41. Epub 2018 Oct 26.

Laboratory of Computational Systems Biotechnology (LCSB), Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland. Electronic address:

Large-scale kinetic models are used for designing, predicting, and understanding the metabolic responses of living cells. Kinetic models are particularly attractive for the biosynthesis of target molecules in cells as they are typically better than other types of models at capturing the complex cellular biochemistry. Using simpler stoichiometric models as scaffolds, kinetic models are built around a steady-state flux profile and a metabolite concentration vector that are typically determined via optimization. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.005DOI Listing
March 2019
17 Reads

Systematically engineering the biosynthesis of a green biosurfactant surfactin by Bacillus subtilis 168.

Authors:
Qun Wu Yan Zhi Yan Xu

Metab Eng 2019 03 16;52:87-97. Epub 2018 Nov 16.

Key Laboratory of Industrial Biotechnology of Ministry of Education, State Key Laboratory of Food Science and Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address:

The biosynthesis of surfactin has attracted broad interest; however, there is a bottleneck in its low yield in wild strains and the ability to engineer Bacillus producers. Because the key metabolic mechanisms in the surfactin synthesis pathway remain unclear, genetic engineering approaches are all ending up with a single or a few gene modifications. The aim of this study is to develop a systematic engineering approach to improve the biosynthesis of surfactin. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183034
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http://dx.doi.org/10.1016/j.ymben.2018.11.004DOI Listing
March 2019
16 Reads
6.770 Impact Factor