Gene disruption analysis of two glycosylation steps in lankamycin biosynthesis in Streptomyces rochei

  • Arakawa Kenji
    Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University
  • Suzuki Toshihiro
    Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University
  • Kinashi Haruyasu
    Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University

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Lankamycin, produced by Streptomyces rochei 7434AN4, is a 14-membered macrolide antibiotic attached with two deoxysugars, 4″-O-acetyl-L-arcanose and D-chalcose. To reveal the order of glycosylation steps in lankamycin biosynthesis, we carried out gene disruption of two glycosyltransferase genes, lkmI and lkmL. The lkmI mutant KA50 produced 3-O-L-arcanosyl lankanolide, while the lkmL mutant KA55 accumulated two aglycons, 8-deoxylankanolide and 8,15-dideoxy-15-oxolankanolide. These results indicated that LkmL transfers L-arcanose to the C-3 hydroxyl of 8-deoxylankanolide, while LkmI does D-chalcose to the C-5 hydroxyl of 3-O-L-arcanosyl lankanolide. Taking together with previous results of gene disruption of two P450 hydroxylases, we propose a biosynthetic pathway of lankamycin including two hydroxylation and two glycosylation steps.

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