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Engineering Streptomyces coelicolor for production of monomethyl branched chain fatty acids

TitleEngineering Streptomyces coelicolor for production of monomethyl branched chain fatty acids
Publication TypeJournal Article
Year of Publication2020
AuthorsYi J.S, Yoo H.W, Kim E.J, Yang Y.H, Kim B.G
Date Published2020/01
Type of ArticleArticle
ISBN Number0168-1656
Accession NumberWOS:000502527100008
Keywordsactinorhodin; antibiotic production; biosynthesis; Biotechnology & Applied Microbiology; Branched chain fatty acids; escherichia-coli; gene-expression; initiation enzyme; polyketide; regulator; replacement; soxr regulon; Streptomyces coelicolor

Branched chain fatty acids (BCFA) are an appealing biorefinery-driven target of fatty acid (FA) production. BCFAs typically have lower melting points compared to straight chain FAs, making them useful in lubricants and biofuels. Actinobacteria, especially Streptomyces species, have unique secondary metabolism that are capable of producing not only antibiotics, but also high percentage of BCFAs in their membrane lipids. Since biosynthesis of polyketide (PK) and FA partially share common pathways to generate acyl-CoA precursors, in theory, Streptomyces sp. with high levels of PK antibiotics production can be easily manipulated into strains producing high levels of BCFAs. To increase the percentage of the BCFA moieties in lipids, we redirected acyl-CoA precursor fluxes from PK into BCFAs using S. coelicolor M1146 (M1146) as a host strain. In addition, 3-ketoacyl acyl carrier protein synthase III and branched chain alpha-keto acid dehydrogenase were overexpressed to push fluxes of branched chain acyl-CoA precursors towards FA synthesis. The maximum titer of 354.1 mg/L BCFAs, 90.3% of the total FA moieties, was achieved using M1146(dD)-B, fadD deletion and bkdABC overexpression mutant of M1146 strain. Cell specific yield of 64.4 mg/L/g(cell) was also achieved. The production titer and specific yield are the highest ever reported in bacterial cells, which provides useful insights to develop an efficient host strain for BCFAs.

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