Modular Organization of Genes Required for Complex Polyketide Biosynthesis

  • Stefano Donadio
    Department of Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.
  • Michael J. Staver
    Department of Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.
  • James B. McAlpine
    Bioactive Microbial Metabolite Project, Abbott Laboratories, Abbott Park, IL 60064.
  • Susan J. Swanson
    Bioactive Microbial Metabolite Project, Abbott Laboratories, Abbott Park, IL 60064.
  • Leonard Katz
    Department of Corporate Molecular Biology, Abbott Laboratories, Abbott Park, IL 60064.

抄録

<jats:p> In <jats:italic>Saccharopolyspora erythraea</jats:italic> , the genes that govern synthesis of the polyketide portion of the macrolide antibiotic erythromycin are organized in six repeated units that encode fatty acid synthase (FAS)-like activities. Each repeated unit is designated a module, and two modules are contained in a single open reading frame. A model for the synthesis of this complex polyketide is proposed, where each module encodes a functional synthase unit and each synthase unit participates specifically in one of the six FAS-like elongation steps required for formation of the polyketide. In addition, genetic organization and biochemical order of events appear to be colinear. Evidence for the model is provided by construction of a selected mutant and by isolation of a polyketide of predicted structure. </jats:p>

収録刊行物

  • Science

    Science 252 (5006), 675-679, 1991-05-03

    American Association for the Advancement of Science (AAAS)

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