caa a22 4500 606213325 CHVBK 20210128101047.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s10295-015-1679-5 doi (NATIONALLICENCE)springer-10.1007/s10295-015-1679-5 Increased valinomycin production in mutants of Streptomyces sp. M10 defective in bafilomycin biosynthesis and branched-chain α-keto acid dehydrogenase complex expression [Elektronische Daten] [Dong Lee, Bee Ng, Beom Kim] Streptomyces sp. M10 is a valinomycin-producing bacterial strain that shows potent bioactivity against Botrytis blight of cucumber plants. During studies to increase the yield of valinomycin (a cyclododecadepsipeptide) in strain M10, additional antifungal metabolites, including bafilomycin derivatives (macrolide antibiotics), were identified. To examine the effect of bafilomycin biosynthesis on valinomycin production, the bafilomycin biosynthetic gene cluster was cloned from the genome of strain M10, as were two branched-chain α-keto acid dehydrogenase (BCDH) gene clusters related to precursor supply for bafilomycin biosynthesis. A null mutant (M10bafm) of one bafilomycin biosynthetic gene (bafV) failed to produce bafilomycin, but resulted in a 1.2- to 1.5-fold increase in the amount of valinomycin produced. In another null mutant (M10bkdFm) of a gene encoding a subunit of the BCDH complex (bkdF), bafilomycin production was completely abolished and valinomycin production increased fourfold relative to that in the wild-type M10 strain. The higher valinomycin yield was likely the result of redistribution of the metabolic flux from bafilomycin to valinomycin biosynthesis, because the two antibiotics share a common precursor, 2-ketoisovaleric acid, a deamination product of valine. The results show that directing precursor flux toward active ingredient biosynthesis could be used as a prospective tool to increase the competence of biofungicides. Society for Industrial Microbiology and Biotechnology, 2015 Antifungal metabolite nationallicence Bafilomycin biofungicide nationallicence Biosynthetic gene cluster nationallicence Branched-chain α-keto acid dehydrogenase nationallicence Streptomyces nationallicence Valinomycin nationallicence Lee Dong Plant Pharmacology Laboratory, Department of Biosystems and Biotechnology, Korea University Graduate School, 136-713, Seoul, Republic of Korea aut Ng Bee Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 136-713, Seoul, Republic of Korea aut Kim Beom Plant Pharmacology Laboratory, Department of Biosystems and Biotechnology, Korea University Graduate School, 136-713, Seoul, Republic of Korea aut Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/11(2015-11-01), 1507-1517 1367-5435 42:11<1507 2015 42 10295 https://doi.org/10.1007/s10295-015-1679-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10295-015-1679-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Dong Plant Pharmacology Laboratory, Department of Biosystems and Biotechnology, Korea University Graduate School, 136-713, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Ng Bee Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, 136-713, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Beom Plant Pharmacology Laboratory, Department of Biosystems and Biotechnology, Korea University Graduate School, 136-713, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Journal of Industrial Microbiology & Biotechnology Springer Berlin Heidelberg 42/11(2015-11-01), 1507-1517 1367-5435 42:11<1507 2015 42 10295