Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively

• Tin-Wein Yu

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Yuemao Shen

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Yukiko Doi-Katayama

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Li Tang

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Cheonseok Park

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Bradley S. Moore

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• C. Richard Hutchinson

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

• Heinz G. Floss

  Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700; and School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison, WI 53706

抄録

The assembly of the polyketide backbone of rifamycin B on the type I rifamycin polyketide synthase (PKS), encoded by the rifA–rifE genes, is terminated by the product of the rifF gene, an amide synthase that releases the completed undecaketide as its macrocyclic lactam. Inactivation of rifF gives a rifamycin B nonproducing mutant that still accumulates a series of linear polyketides ranging from the tetra- to a decaketide, also detected in the wild type, demonstrating that the PKS operates in a processive manner. Disruptions of the rifD module 8 and rifE module 9 and module 10 genes also result in accumulation of such linear polyketides as a consequence of premature termination of polyketide assembly. Whereas the tetraketide carries an unmodified aromatic chromophore, the penta- through decaketides have undergone oxidative cyclization to the naphthoquinone, suggesting that this modification occurs during, not after, PKS assembly. The structure of one of the accumulated compounds together with 18 O experiments suggests that this oxidative cyclization produces an 8-hydroxy-7,8-dihydronaphthoquinone structure that, after the stage of proansamycin X, is dehydrogenated to an 8-hydroxynaphthoquinone.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 96 (16), 9051-9056, 1999-08-03

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360855570807162240
• NII論文ID: 80011256222
• DOI: 10.1073/pnas.96.16.9051
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.96.16.9051
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