Metabolic engineering of Escherichia coli for 1,3-butanediol biosynthesis through the inverted fatty acid β-oxidation cycle

Gulevich, A. Yu.; Skorokhodova, A. Yu.; Stasenko, A. A.; Шакулов, Р. С.; Дебабов, В. Г.

doi:10.1134/s0003683816010051

Cited by 14 publications

(11 citation statements)

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“…focused on the biotransformation of 4-hydroxy-2-butanone [123][124][125] or 1,3-BDO racemic mixture [126][127][128] to (R)-1,3-BDO. More recently, two artificial metabolic pathways for (R)-1,3-BDO production from glucose have been developed: (i) the reversed fatty acid β-oxidation pathway [129][130][131] and (ii) the 2-deoxyribose-5-phosphate aldolasealdo-keto reductase (DERA-AKR) pathway. [33,132] The first route for 1,3-BDO production is the conversion of BDO was produced via fed-batch fermentation under optimized culture conditions.…”

Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

“…[130] In another study, given the oxygen-sensitive nature of butyryl-CoA dehydrogenase, the feasibility of anaerobic 1,3-BDO production was evaluated. [131] A pathway was constructed in 1-butanol-producing E. coli by overexpressing atoB (acetyl-CoA acetyltransferase), fucO (alcohol dehydrogenase), and yqhD (alcohol dehydrogenase). Additional overexpression of the aceEF and lpdA operon genes and the inactivation of fadE and ydiO led to the anaerobic synthesis of 1,3-BDO with a final titer of 0.027 g L -1 .…”

Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

“…Additional overexpression of the aceEF and lpdA operon genes and the inactivation of fadE and ydiO led to the anaerobic synthesis of 1,3-BDO with a final titer of 0.027 g L -1 . [131] The second pathway has been designed based on aldolase chemistry and consists of three steps: (i) the production of two acetaldehyde molecules using pyruvate decarboxylase, (ii) the condensation of acetaldehydes to 3-hydroxybutanal using DERA, and (iii) the reduction of 3-hydroxybutanal to 1,3-BDO using AKR. Based on this pathway, E.…”

Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

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Recent advances in the microbial production of C4 alcohols by metabolically engineered microorganisms

Yoo

Sohn

Son

et al. 2021

Biotechnology Journal

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Background:The heavy global dependence on petroleum-based industries has led to serious environmental problems, including climate change and global warming. As a result, there have been calls for a paradigm shift towards the use of biorefineries, which employ natural and engineered microorganisms that can utilize various carbon sources from renewable resources as host strains for the carbon-neutral production of target products.Purpose and Scope: C4 alcohols are versatile chemicals that can be used directly as biofuels and bulk chemicals and in the production of value-added materials such as plastics, cosmetics, and pharmaceuticals. C4 alcohols can be effectively produced by microorganisms using DCEO biotechnology (tools to design, construct, evaluate, and optimize) and metabolic engineering strategies. Summary of New Synthesis and Conclusions:In this review, we summarize the production strategies and various synthetic tools available for the production of C4 alcohols and discuss the potential development of microbial cell factories, including the optimization of fermentation processes, that offer cost competitiveness and potential industrial commercialization.

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Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

Section: Metabolic Engineering For the Production Of Non-natural-non-...mentioning

confidence: 99%

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Recent advances in the microbial production of C4 alcohols by metabolically engineered microorganisms

Yoo

Sohn

Son

et al. 2021

Biotechnology Journal

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“…At the same time, the clostridial reactions of 1-butanol biosynthesis, from the biochemical point of view, are similar to the reversed reactions of the fatty acid β-oxidation (FABO) cycle, a biochemical pathway present in many microorganisms. The functional reversal of FABO was experimentally shown in a number of studies demonstrating the production from glucose or glycerol of various chain-length aliphatic carboxylic acids and alcohols, through this pathway, by recombinant E. coli strains [9][10][11][12]. Consequently, (S)-3-HBA can be synthesized by E. coli from glucose resulting from a partial one-turn reversal of FABO upon overexpression of a suitable thioesterase without the necessity of using any foreign genes.…”

Section: Introductionmentioning

confidence: 97%

Optimization of (S)-3-Hydroxybutyric Acid Biosynthesis from Glucose through the Reversed Fatty Acid β-Oxidation Pathway by Recombinant Escherichia coli Strains

Gulevich

Skorokhodova

Дебабов

2021

Appl Biochem Microbiol

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The microaerobic synthesis of 3-hydroxybutyric acid by the Escherichia coli strain BOX3.1 ∆4 PL-atoB PL-tesB (MG1655 lacIQ, ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, ∆fadE, PL-SDphi10-atoB, Ptrc-ideal-4-SDphi10-fadB, PL-SDphi10-tesB), which was previously directly engineered for the biosynthesis of the target compound from glucose through the reversed fatty acid β-oxidation pathway, was studied. A target product yield of 0.12 mol/mol was achieved. Inactivation of the nonspecific YciA thioesterase gene in the strain led to an increase in the yield of 3-hydroxybutyric acid to 0.15 mol/mol. For the optimization of biosynthesis of target product the strain MG∆4 PL-tesB (MG1655 ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, PL-SDphi10-tesB) was engineered, and the genes encoding key enzymes of fatty acid β-oxidation were overexpressed in the strain from the plasmid pMW118m-atoB-fadB. The level of microaerobic synthesis of 3-hydroxybutyric acid by the strain MG∆4 PL-tesB (pMW118m-atoB-fadB) achieved in primary evaluation conditions reached 0.35 mol/mol. Inactivation in the strain of the gene of nonspecific thioesterase YciA led to only minor decrease in acetate byproduction. Further inactivation in the strain of gene encoding nonspecific thioesterase YdiI had virtually no effect on the level of synthesis of side products. Cultivation of the constructed strain MG∆4 PL-tesB ∆yciA (pMW118m-atoB-fadB) in bioreactor under the controlled conditions ensured achievement of a yield of 3‑hydroxybutyric acid amounting to 0.75 mol/mol.

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“…For example, the α,β-unsaturated and 3-functionalized alcohols have only been produced through the isoprenoid pathway or the reversed β-oxidation pathway. 8,9 Furthermore, some configurations, such as the tertiary branched-alcohols, have not been produced in biomanufacturing, despite their important applications as fuel additives and solvents. 10 Due to their bulky and hydrophobic nature, tertiary branched-compounds, such as tert-leucine, are essential reagents for molecular conformational control in chemical synthesis.…”

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confidence: 99%

Engineering a Coenzyme A Detour To Expand the Product Scope and Enhance the Selectivity of the Ehrlich Pathway

et al. 2018

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The Ehrlich pathway is a major route for the renewable production of higher alcohols. However, the product scope of the Ehrlich pathway is restricted, and the product selectivity is suboptimal. Here, we demonstrate that a Coenzyme A (CoA) detour, which involves conversion of the 2-keto acids into acyl-CoAs, expands the biological toolkit of reaction chemistries available in the Ehrlich pathway to include the gamut of CoA-dependent enzymes. As a proof-of-concept, we demonstrated the first biosynthesis of a tertiary branched-alcohol, pivalcohol, at a level of ~10 mg/L from glucose in Escherichia coli, using a pivalyl-CoA mutase from Xanthobacter autotrophicus. Furthermore, engineering an enzyme in the CoA detour, the Lactobacillus brevis CoA-acylating aldehyde dehydrogenase, allowed stringent product selectivity. Targeted production of 3-methyl-1-butanol (3-MB) in E. coli mediated by the CoA detour showed a 3-MB:side-product (isobutanol) ratio of >20, an increase over the ratios previously achieved using the conventional Ehrlich pathway.

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Metabolic engineering of Escherichia coli for 1,3-butanediol biosynthesis through the inverted fatty acid β-oxidation cycle

Cited by 14 publications

References 14 publications

Recent advances in the microbial production of C4 alcohols by metabolically engineered microorganisms

Recent advances in the microbial production of C4 alcohols by metabolically engineered microorganisms

Optimization of (S)-3-Hydroxybutyric Acid Biosynthesis from Glucose through the Reversed Fatty Acid β-Oxidation Pathway by Recombinant Escherichia coli Strains

Engineering a Coenzyme A Detour To Expand the Product Scope and Enhance the Selectivity of the Ehrlich Pathway

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