Regulatory and biosynthetic effects of the bkd gene clusters on the production of daptomycin and its analogs A21978C1–3

Regulatory and biosynthetic effects of the bkd gene clusters on the production of daptomycin and... Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus in an acidic peptide complex A21978C. In this complex, A21978C1–3 is most abundant and contains branched-chain fatty acyl groups, while daptomycin has a straight decanoic acyl group. The branched-chain α-keto acid dehydrogenase complex (BCDH complex), encoded by bkd gene clusters in Streptomyces, is responsible for the early step of converting branched-chain amino acids into branched-chain fatty acids. In a daptomycin industrial producer S. roseosporus L30, two alleles of bkd gene clusters, bkdA1B1C1/bkdA2B2C2, and a regulatory gene bkdR located upstream of bkdA2B2C2 are identified. We show that BkdR positively regulated bkdA2B2C2 expression and was negatively auto-regulated, but is not directly involved in regulation of daptomycin gene cluster expression. However, BkdR is required for both daptomycin and A21978C1–3 production. Furthermore, deletion of bkdA2B2C2 only led to partial reduction of A21978C1–3 production, while the ΔbkdA1B1C1 mutant shows very weak production of A21978C1–3, and the double bkd mutant has a similar production profile as the single ΔbkdA1B1C1 mutant, suggesting that bkdA1B1C1 gene cluster plays a dominant role in branched-chain fatty acid biosynthesis. So we reveal a unique regulatory function of BkdR and genetic engineered a bkd null strain for daptomycin production with reduced impurities. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Industrial Microbiology Biotechnology Springer Journals

Regulatory and biosynthetic effects of the bkd gene clusters on the production of daptomycin and its analogs A21978C1–3

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Publisher
Springer International Publishing
Copyright
Copyright © 2018 by Society for Industrial Microbiology and Biotechnology
Subject
Life Sciences; Microbiology; Biochemistry, general; Inorganic Chemistry; Genetic Engineering; Biotechnology; Bioinformatics
ISSN
1367-5435
eISSN
1476-5535
D.O.I.
10.1007/s10295-018-2011-y
Publisher site
See Article on Publisher Site

Abstract

Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus in an acidic peptide complex A21978C. In this complex, A21978C1–3 is most abundant and contains branched-chain fatty acyl groups, while daptomycin has a straight decanoic acyl group. The branched-chain α-keto acid dehydrogenase complex (BCDH complex), encoded by bkd gene clusters in Streptomyces, is responsible for the early step of converting branched-chain amino acids into branched-chain fatty acids. In a daptomycin industrial producer S. roseosporus L30, two alleles of bkd gene clusters, bkdA1B1C1/bkdA2B2C2, and a regulatory gene bkdR located upstream of bkdA2B2C2 are identified. We show that BkdR positively regulated bkdA2B2C2 expression and was negatively auto-regulated, but is not directly involved in regulation of daptomycin gene cluster expression. However, BkdR is required for both daptomycin and A21978C1–3 production. Furthermore, deletion of bkdA2B2C2 only led to partial reduction of A21978C1–3 production, while the ΔbkdA1B1C1 mutant shows very weak production of A21978C1–3, and the double bkd mutant has a similar production profile as the single ΔbkdA1B1C1 mutant, suggesting that bkdA1B1C1 gene cluster plays a dominant role in branched-chain fatty acid biosynthesis. So we reveal a unique regulatory function of BkdR and genetic engineered a bkd null strain for daptomycin production with reduced impurities.

Journal

Journal of Industrial Microbiology BiotechnologySpringer Journals

Published: Feb 7, 2018

References

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