Increased valinomycin production in mutants of Streptomyces sp. M10 defective in bafilomycin biosynthesis and branched-chain [alpha]-keto acid dehydrogenase complex expression

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 derivativ...

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Bibliographic Details
Published in:Journal of industrial microbiology & biotechnology 2015-11, Vol.42 (11), p.1507
Main Authors: Lee, Dong Wan, Ng, Bee Gek, Kim, Beom Seok
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Biological activity
Biosynthesis
Biotechnology
Cell culture
Cloning
Dehydrogenase
Dehydrogenases
E coli
Fermentation
Fungi
Gene expression
Genetic engineering
Genomics
Metabolism
Metabolites
Microbiology
NMR
Nuclear magnetic resonance
Peptides
Plant diseases
Studies
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Summary: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 [alpha]-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.
ISSN:1367-5435
1476-5535
DOI:10.1007/s10295-015-1679-5