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Title: Identification of the bkdAB gene cluster, a plausible source of the starter-unit for virginiamycin M production in Streptomyces virginiae
Authors: Nattika Pulsawat
Shigeru Kitani
Hiroshi Kinoshita
Chang Kwon Lee
Takuya Nihira
Osaka University
College of Medicine and Institute of Biomedical Science and Technology
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 1-Jun-2007
Citation: Archives of Microbiology. Vol.187, No.6 (2007), 459-466
Abstract: The bkdAB gene cluster, which encodes plausible E1 and E2 components of the branched-chain α-keto acid dehydrogenase (BCDH) complex, was isolated from Streptomyces virginiae in the vicinity of a regulatory island for virginiamycin production. Gene disruption of bkdA completely abolished the production of virginiamycin M (a polyketide-peptide antibiotic), while the production of virginiamycin S (a cyclodepsipeptide antibiotic) was unaffected. Complementation of the bkdA disruptant by genome-integration of intact bkdA completely restored the virginiamycin M production, indicating that the bkdAB cluster is essential for virginiamycin M biosynthesis, plausibly via the provision of isobutyryl-CoA as a primer unit. In contrast to a feature usually seen in the Streptomyces E1 component, namely, the separate encoding of the α and β subunits, S. virginiae bkdA seemed to encode the fused form of the α and β subunits, which was verified by the actual catalytic activity of the fused protein in vitro using recombinant BkdA overexpressed in Escherichia coli. Supply of an additional bkdA gene under the strong and constitutive promoter ermE*in the wild-type strain of S. virginiae resulted in enhanced production of virginiamycin M, suggesting that the supply of isobutyryl-CoA is one of the rate-limiting factors in the biosynthesis of virginiamycin M. © 2007 Springer-Verlag.
ISSN: 03028933
Appears in Collections:Scopus 2006-2010

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