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Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid.

ABSTRACT: 1,2-propanediol (1,2-PDO) is an industrial chemical with a broad range of applications, such as the production of alkyd and unsaturated polyester resins. It is currently produced as a racemic mixture from nonrenewable petroleum-based feedstocks. We have reported a novel artificial pathway for the biosynthesis of 1,2-PDO via lactic acid isomers as the intermediates. The pathway circumvents the cytotoxicity issue caused by methylglyoxal intermediate in the naturally existing pathway. Successful E. coli bioconversion of lactic acid to 1,2-PDO was shown in previous report. Here, we demonstrated the engineering of E. coli host strains for the de novo biosynthesis of 1,2-PDO through this pathway. Under fermenter-controlled conditions, the R-1,2-PDO was produced at 17.3?g/L with a molar yield of 42.2% from glucose, while the S-isomer was produced at 9.3?g/L with a molar yield of 23.2%. The optical purities of the two isomers were 97.5% ee (R) and 99.3% ee (S), respectively. To the best of our knowledge, these are the highest titers of 1,2-PDO biosynthesized by either natural producer or engineered microbial strains that are published in peer-reviewed journals.

SUBMITTER: Niu W

PROVIDER: S-EPMC6304458 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Metabolic engineering of <i>Escherichia coli</i> for the <i>de novo</i> stereospecific biosynthesis of 1,2-propanediol through lactic acid.

Niu Wei W Kramer Levi L Mueller Joshua J Liu Kun K Guo Jiantao J

Metabolic engineering communications 20181123

1,2-propanediol (1,2-PDO) is an industrial chemical with a broad range of applications, such as the production of alkyd and unsaturated polyester resins. It is currently produced as a racemic mixture from nonrenewable petroleum-based feedstocks. We have reported a novel artificial pathway for the biosynthesis of 1,2-PDO via lactic acid isomers as the intermediates. The pathway circumvents the cytotoxicity issue caused by methylglyoxal intermediate in the naturally existing pathway. Successful <i ...[more]

PMID: 30591904

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Project description:BackgroundResveratrol is a plant secondary metabolite with diverse, potential health-promoting benefits. Due to its nutraceutical merit, bioproduction of resveratrol via microbial engineering has gained increasing attention and provides an alternative to unsustainable chemical synthesis and straight extraction from plants. However, many studies on microbial resveratrol production were implemented with the addition of water-insoluble phenylalanine or tyrosine-based precursors to the medium, limiting in the sustainable development of bioproduction.ResultsHere we present a novel coculture platform where two distinct metabolic background species were modularly engineered for the combined total and de novo biosynthesis of resveratrol. In this scenario, the upstream Escherichia coli module is capable of excreting p-coumaric acid into the surrounding culture media through constitutive overexpression of codon-optimized tyrosine ammonia lyase from Trichosporon cutaneum (TAL), feedback-inhibition-resistant 3-deoxy-d-arabinoheptulosonate-7-phosphate synthase (aroGfbr) and chorismate mutase/prephenate dehydrogenase (tyrAfbr) in a transcriptional regulator tyrR knockout strain. Next, to enhance the precursor malonyl-CoA supply, an inactivation-resistant version of acetyl-CoA carboxylase (ACC1S659A,S1157A) was introduced into the downstream Saccharomyces cerevisiae module constitutively expressing codon-optimized 4-coumarate-CoA ligase from Arabidopsis thaliana (4CL) and resveratrol synthase from Vitis vinifera (STS), and thus further improve the conversion of p-coumaric acid-to-resveratrol. Upon optimization of the initial inoculation ratio of two populations, fermentation temperature, and culture time, this co-culture system yielded 28.5 mg/L resveratrol from glucose in flasks. In further optimization by increasing initial net cells density at a test tube scale, a final resveratrol titer of 36 mg/L was achieved.ConclusionsThis is first study that demonstrates the use of a synthetic E. coli-S. cerevisiae consortium for de novo resveratrol biosynthesis, which highlights its potential for production of other p-coumaric-acid or resveratrol derived biochemicals.

Dataset Information

Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid.

Publications

Metabolic engineering of <i>Escherichia coli</i> for the <i>de novo</i> stereospecific biosynthesis of 1,2-propanediol through lactic acid.

Similar Datasets

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