1,388 results match your criteria Metabolic Engineering [Journal]


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

Metab Eng 2019 Feb 7. 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
February 2019

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

Metab Eng 2019 Jan 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
January 2019
3 Reads
6.767 Impact Factor

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

Metab Eng 2019 Jan 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
January 2019

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

Metab Eng 2019 Mar 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
9 Reads

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

Metab Eng 2019 Mar 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

Continuous translation of circularized mRNA improves recombinant protein titer.

Metab Eng 2019 Mar 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 Mar 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
5 Reads

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

Metab Eng 2019 Mar 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 2018 Dec 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
December 2018

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

Metab Eng 2019 Mar 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
1 Read

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

Metab Eng 2019 Mar 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 Mar 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

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

Metab Eng 2019 Mar 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
15 Reads

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

Metab Eng 2019 Mar 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 Mar 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 Mar 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
1 Read
6.767 Impact Factor

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

Metab Eng 2019 Mar 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 Mar 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 Mar 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
13 Reads

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

Metab Eng 2019 Mar 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
7 Reads

Regulatory non-coding sRNAs in bacterial metabolic pathway engineering.

Metab Eng 2019 Mar 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
6 Reads

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

Metab Eng 2019 Mar 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 Mar 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
14 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 Mar 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
14 Reads

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

Metab Eng 2019 Mar 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
25 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
8 Reads

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

Metab Eng 2019 Mar 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 Mar 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
11 Reads

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

Authors:
Qun Wu Yan Zhi Yan Xu

Metab Eng 2019 Mar 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
12 Reads
6.770 Impact Factor

Improving recombinant bone morphogenetic protein-4 (BMP-4) production by autoregulatory feedback loop removal using BMP receptor-knockout CHO cell lines.

Metab Eng 2019 Mar 14;52:57-67. Epub 2018 Nov 14.

Department of Biological Sciences, KAIST, Daejeon, Republic of Korea; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark. Electronic address:

A Chinese hamster ovary (CHO) cell line producing recombinant human bone morphogenetic protein-4 (rhBMP-4) (CHO-BMP-4), which expresses essential components of BMP signal transduction, underwent autocrine BMP-4 signaling. RNA seq analysis on CHO host cells (DG44) treated with rhBMP-4 (20 µg/mL) suggested that rhBMP-4 induced signaling in CHO cells could be a critical factor in limiting rhBMP-4 production and should be removed to improve rhBMP-4 production in recombinant CHO (rCHO) cells. The inhibition of autocrine BMP signaling in CHO-BMP-4 cells by the addition of LDN-193189, a chemical inhibitor of BMP receptor type I, significantly increased the mRNA expression levels of rhBMP-4. 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.2018.11.003DOI Listing
March 2019
15 Reads

Combining retinal-based and chlorophyll-based (oxygenic) photosynthesis: Proteorhodopsin expression increases growth rate and fitness of a ∆PSI strain of Synechocystis sp. PCC6803.

Metab Eng 2019 Mar 14;52:68-76. Epub 2018 Nov 14.

Molecular Microbial Physiology, Swammerdam Institute for Life Sciences, University of Amsterdam, the Netherlands. Electronic address:

To fill the "green absorption gap", a green absorbing proteorhodopsin was expressed in a PSI-deletion strain (ΔPSI) of Synechocystis sp. PCC6803. Growth-rate measurements, competition experiments and physiological characterization of the proteorhodopsin-expressing strains, relative to the ΔPSI control strain, allow us to conclude that proteorhodopsin can enhance the rate of photoheterotrophic growth of ΔPSI Synechocystis strain. 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.2018.11.002DOI Listing
March 2019
8 Reads

Predicting the metabolic capabilities of Synechococcus elongatus PCC 7942 adapted to different light regimes.

Metab Eng 2019 Mar 13;52:42-56. Epub 2018 Nov 13.

Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA. Electronic address:

There is great interest in engineering photoautotrophic metabolism to generate bioproducts of societal importance. Despite the success in employing genome-scale modeling coupled with flux balance analysis to engineer heterotrophic metabolism, the lack of proper constraints necessary to generate biologically realistic predictions has hindered broad application of this methodology to phototrophic metabolism. Here we describe a methodology for constraining genome-scale models of photoautotrophy in the cyanobacteria Synechococcus elongatus PCC 7942. 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.2018.11.001DOI Listing
March 2019
11 Reads

Rewiring metabolic network by chemical modulator based laboratory evolution doubles lipid production in Crypthecodinium cohnii.

Metab Eng 2019 01 26;51:88-98. Epub 2018 Oct 26.

Laboratory of Synthetic Microbiology, School of Chemical Engineering & Technology, Tianjin University, Tianjin, PR China; Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, PR China; SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, PR China; Center for Biosafety Research and Strategy, Tianjin University, Tianjin, PR China. Electronic address:

Dietary omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA, C22:6) can be synthesized in microalgae Crypthecodinium cohnii; however, its productivity is still low. Here, we established a new protocol termed as "chemical modulator based adaptive laboratory evolution" (CM-ALE) to enhance lipid and DHA productivity in C. cohnii. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183026
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http://dx.doi.org/10.1016/j.ymben.2018.10.004DOI Listing
January 2019
9 Reads

Direct cell-to-cell exchange of matter in a synthetic Clostridium syntrophy enables CO fixation, superior metabolite yields, and an expanded metabolic space.

Metab Eng 2019 Mar 2;52:9-19. Epub 2018 Nov 2.

Department of Chemical and Biomolecular Engineering, University of Delaware, 15 Innovation Way, Newark, DE 19711, USA; Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE 19711, USA. Electronic address:

In microbial fermentations at least 33% of the sugar-substrate carbon is lost as CO during pyruvate decarboxylation to acetyl-CoA, with the corresponding electrons lost in the form of H. Previous attempts to reduce this carbon and electron loss focused on engineering of a single organism. In nature, most microorganisms live in complex communities where syntrophic interactions result in superior resource utilization. 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.2018.10.006DOI Listing
March 2019
7 Reads

Upgrade of wood sugar d-xylose to a value-added nutraceutical by in vitro metabolic engineering.

Metab Eng 2019 Mar 31;52:1-8. Epub 2018 Oct 31.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin Airport Economic Area, Tianjin 300308, China. Electronic address:

The upgrade of D-xylose, the most abundant pentose, to value-added biochemicals is economically important to next-generation biorefineries. myo-Inositol, as vitamin B8, has a six-carbon carbon-carbon ring. Here we designed an in vitro artificial NAD(P)-free 12-enzyme pathway that can effectively convert the five-carbon xylose to inositol involving xylose phosphorylation, carbon-carbon (C-C) rearrangement, C-C bond circulation, and dephosphorylation. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.007DOI Listing
March 2019
18 Reads

Increased sesqui- and triterpene production by co-expression of HMG-CoA reductase and biotin carboxyl carrier protein in tobacco (Nicotiana benthamiana).

Metab Eng 2019 Mar 31;52:20-28. Epub 2018 Oct 31.

Department of Biological Sciences, University of Calgary, Calgary, AB, T2N1N4, Canada. Electronic address:

Terpenoids are the most diverse natural products with many industrial applications and are all synthesized from simple precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). In plants, IPP is synthesized by two distinct metabolic pathways - cytosolic mevalonate (MVA) pathway for C15 sesquiterpene and C30 triterpene, and plastidic methylerythritol phosphate (MEP) pathway for C10 monoterpene and C20 diterpene. A number of studies have altered the metabolic gene expressions in either the MVA or MEP pathway to increase terpene production; however, it remains unknown if the alteration of the acetyl-CoA pool in plastid fatty acid biosynthesis can influence terpenoid flux. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.008DOI Listing
March 2019
12 Reads

Expanding biological applications using cell-free metabolic engineering: An overview.

Authors:
James R Swartz

Metab Eng 2018 11 25;50:156-172. Epub 2018 Oct 25.

Department of Chemical Engineering, Stanford University, 443 Via Ortega, Stanford, CA 95305-4300, USA; Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA 95305-4300, USA. Electronic address:

Expanding the concept of cell-free biology, implemented both with purified components and crude extracts, is continuing to deepen our appreciation of biological fundamentals while enlarging the range of applications. We are no longer intimidated by the complexity of crude extracts and complicated reaction systems with hundreds of active components, and, instead, coordinately activate and inactivate metabolic processes to focus and expand the capabilities of natural biological processes. This, in turn, dramatically increases the range of benefits offered by new products, both natural and supernatural, that were previously infeasible and/or unimaginable. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.011DOI Listing
November 2018
19 Reads

Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis.

Metab Eng 2019 01 19;51:59-69. Epub 2018 Oct 19.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China. Electronic address:

One of the primary goals of microbial metabolic engineering is to achieve high titer, yield and productivity (TYP) of engineered strains. This TYP index requires optimized carbon flux toward desired molecule with minimal by-product formation. De novo redesign of central carbon and redox metabolism holds great promise to alleviate pathway bottleneck and improve carbon and energy utilization efficiency. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.002DOI Listing
January 2019

Efficient production of 3-hydroxypropionate from fatty acids feedstock in Escherichia coli.

Metab Eng 2019 01 19;51:121-130. Epub 2018 Oct 19.

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

The production of chemicals from renewable biomass resources is usually limited by factors including high-cost processes and low efficiency of biosynthetic pathways. Fatty acids (FAs) are an ideal alternative biomass. Their advantages include high-efficiently producing acetyl-CoA and reducing power, coupling chemical production with CO fixation, and the fact that they are readily obtained from inexpensive feedstocks. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.003DOI Listing
January 2019
11 Reads

Identification of a novel cytochrome P450 enzyme that catalyzes the C-2α hydroxylation of pentacyclic triterpenoids and its application in yeast cell factories.

Metab Eng 2019 01 16;51:70-78. Epub 2018 Oct 16.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China; Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, China. Electronic address:

C-2α hydroxylated triterpenoids are a large class of plant secondary metabolites. These compounds, such as maslinic, corosolic and alphitolic acid, have important biological activities against HIV, cancer and diabetes. However, the biosynthesis pathways of these compounds have not been completely elucidated. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.10.001DOI Listing
January 2019
1 Read

Biosynthesis of monoethylene glycol in Saccharomyces cerevisiae utilizing native glycolytic enzymes.

Metab Eng 2019 01 27;51:20-31. Epub 2018 Sep 27.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States. Electronic address:

Monoethylene glycol (MEG) is an important commodity chemical with applications in numerous industrial processes, primarily in the manufacture of polyethylene terephthalate (PET) polyester used in packaging applications. In the drive towards a sustainable chemical industry, bio-based production of MEG from renewable biomass has attracted growing interest. Recent attempts for bio-based MEG production have investigated metabolic network modifications in Escherichia coli, specifically rewiring the xylose assimilation pathways for the synthesis of MEG. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.012DOI Listing
January 2019
16 Reads

Secondary metabolites overproduction through transcriptional gene cluster refactoring.

Metab Eng 2018 09 18;49:299-315. Epub 2018 Sep 18.

Department Microbial Natural Products, Actinobacteria Metabolic Engineering Group, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infectious Research (HZI), Germany. Electronic address:

We present a random rational approach enabling the construction of overproducing strains in two steps. The approach first involves creating a library of clusters of interest, in which native promoters are substituted with randomly generated constitutive synthetic promoters, and then expressing this library in an appropriate host strain. This strategy is fast, easy to use, accounts for the architecture of a cluster and completely decouples the expression of a gene cluster from complex native regulatory networks. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183028
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http://dx.doi.org/10.1016/j.ymben.2018.09.010DOI Listing
September 2018
17 Reads

Application of a curated genome-scale metabolic model of CHO DG44 to an industrial fed-batch process.

Metab Eng 2019 01 15;51:9-19. Epub 2018 Sep 15.

Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800 Kgs, Lyngby, Denmark. Electronic address:

CHO cells have become the favorite expression system for large scale production of complex biopharmaceuticals. However, industrial strategies for upstream process development are based on empirical results, due to a lack of fundamental understanding of intracellular activities. Genome scale models of CHO cells have been reconstructed to provide an economical way of analyzing and interpreting large-omics datasets, since they add cellular context to the data. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.009DOI Listing
January 2019
3 Reads

High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep metabolic engineering.

Metab Eng 2018 09 14;49:287-298. Epub 2018 Sep 14.

National and Local United Engineering Lab of Metabolic Control Fermentation Technology, Tianjin University of Science and Technology, Tianjin 300457, China; Key Laboratory of Industrial Microbiology of the Ministry of Education, Tianjin 300457, China; College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address:

4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic activity and is a promising candidate for the treatment of diabetes. Direct fermentation of 4-HIL has been recently studied; however, the expected titre and yield were not achieved. In this study, we initially developed a pathway for the synthesis of 4-HIL in an L-isoleucine producer, C. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.008DOI Listing
September 2018
7 Reads

Engineering NADH/NAD ratio in Halomonas bluephagenesis for enhanced production of polyhydroxyalkanoates (PHA).

Metab Eng 2018 09 13;49:275-286. Epub 2018 Sep 13.

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

Halomonas bluephagenesis has been developed as a platform strain for the next generation industrial biotechnology (NGIB) with advantages of resistances to microbial contamination and high cell density growth (HCD), especially for production of polyhydroxyalkanoates (PHA) including poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). However, little is known about the mechanism behind PHA accumulation under oxygen limitation. This study for the first time found that H. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.007DOI Listing
September 2018

Characterization of the Clostridium thermocellum AdhE, NfnAB, ferredoxin and Pfor proteins for their ability to support high titer ethanol production in Thermoanaerobacterium saccharolyticum.

Metab Eng 2019 01 12;51:32-42. Epub 2018 Sep 12.

Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA; Center for Bioenergy Innovation, Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA; Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA. Electronic address:

The thermophilic anaerobes Thermoanaerobacterium saccharolyticum and Clostridium thermocellum are good candidates for lignocellulosic ethanol production. T. saccharolyticum has been successfully engineered to produce ethanol at high titer (70 g/L). Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.006DOI Listing
January 2019

Engineering Saccharomyces cerevisiae for production of simvastatin.

Metab Eng 2019 01 10;51:1-8. Epub 2018 Sep 10.

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, United States. Electronic address:

Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvastatin from a microbial host. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348118PMC
January 2019

Multiobjective strain design: A framework for modular cell engineering.

Metab Eng 2019 01 7;51:110-120. Epub 2018 Sep 7.

Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, TN, 37996 United States; Center for Bioenergy Innovation, Oak Ridge National Laboratory, Oak Ridge, TN, United States. Electronic address:

Diversity of cellular metabolism can be harnessed to produce a large space of molecules. However, development of optimal strains with high product titers, rates, and yields required for industrial production is laborious and expensive. To accelerate the strain engineering process, we have recently introduced a modular cell design concept that enables rapid generation of optimal production strains by systematically assembling a modular cell with an exchangeable production module(s) to produce target molecules efficiently. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183025
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http://dx.doi.org/10.1016/j.ymben.2018.09.003DOI Listing
January 2019
2 Reads

Generation of a cluster-free Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters.

Metab Eng 2018 09 6;49:316-324. Epub 2018 Sep 6.

Pharmazeutische Biotechnologie, Universität des Saarlandes, Saarbrücken, Germany; Helmholtz-Institut für Pharmazeutische Forschung Saarland, Saarbrücken, Germany. Electronic address:

Natural products are a rich source of potential drugs for many applications. Discovery of natural products through the activation of cryptic gene clusters encoding their biosynthetic pathways, engineering of those biosynthetic pathways and optimization of production yields often rely on the expression of these gene clusters in suitable heterologous host strains. Streptomyces albus J1074 provides high success rates of heterologous cluster expression with high levels of metabolite production, rapid growth and amenability to genetic manipulations. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967176183028
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http://dx.doi.org/10.1016/j.ymben.2018.09.004DOI Listing
September 2018
18 Reads

Engineering a spermidine biosynthetic pathway in Clostridium thermocellum results in increased resistance to furans and increased ethanol production.

Metab Eng 2018 09 5;49:267-274. Epub 2018 Sep 5.

Department of Genetics, University of Georgia, Athens, GA 30602, USA; Oak Ridge National Laboratory, The BioEnergy Science Center and the Center for Bioenergy Innovation, Oak Ridge, TN 37831, USA. Electronic address:

Polyamines are low molecular weight aliphatic nitrogen compounds found ubiquitously in microorganisms, plants, and animals. Spermidine is a common polyamine that plays a role in stabilizing chromatin, DNA replication, transcription, translation, as well as the regulation of cell growth and apoptosis in eukaryotes. Amines are also associated with defense to a number of environmental stresses including elevated temperature and have been shown to be involved in tolerance to fermentation inhibitors such as furan derivatives and acetic acid in Saccharomyces cerevisiae. Read More

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http://dx.doi.org/10.1016/j.ymben.2018.09.002DOI Listing
September 2018
5 Reads