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영어

Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Previously, we isolated and characterized the entire TMC biosynthetic gene cluster from
Streptomyces sp. CK44121). And also, TMC pathway-specific gene, tmcN was successfully utilized to increase TMC productivity by introducing its extra copies, implying the importance of the regulatory network optimization for strain improvement2). It was previously reported that a 64-
amino-acid encoding wblA inhibited the biosynthesis of doxorubicin in S. peucetius as well as the antibiotics production in S. coelicolor, suggesting that wblA and its homologs act globally among streptomycetes as putative down-regulators of antibiotic biosynthesis3). Here, we identified a wblA ortholog gene (named wblA-tmc) via genomic DNA library screening using the degenerated primers based on wblA sequence from S. coelicolor A3(2). A 0.39kb wblA-tmc showed 96% amino acid identity compared to a previously-known S. coelicolor wblA. A targeted gene disruption of wblAtmc from the TMC-producing strain, which was confirmed by PCR and
Southern-hybridization, exhibited significantly different morphological pattern as well as TMC productivity.. The more detailed biological significance of wblA-tmc will be discussed.