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Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization

Author

Listed:
  • Jason M. Crawford

    (Department of Chemistry,)

  • Tyler P. Korman

    (Department of Molecular Biology and Biochemistry,)

  • Jason W. Labonte

    (Department of Chemistry,)

  • Anna L. Vagstad

    (Department of Chemistry,)

  • Eric A. Hill

    (Department of Chemistry,)

  • Oliver Kamari-Bidkorpeh

    (Department of Chemistry,)

  • Shiou-Chuan Tsai

    (Department of Molecular Biology and Biochemistry,
    Department of Chemistry,
    University of California, Irvine, California 92697, USA)

  • Craig A. Townsend

    (Department of Chemistry,
    Department of Biology,
    Johns Hopkins University, Maryland 21218, USA)

Abstract

Fungal toxin biosynthesis Polyketides are a class of natural products with diverse structures and biological activities. Here, Jason Crawford and colleagues report the X-ray crystal structure of a domain of the iterative polyketide synthase that is responsible for generating the potent hepatocarcinogen aflatoxin B1. This domain — called the product template (PT) domain – catalyses the stepwise intramolecular aldol cyclizations and their dehydrations to yield a bicyclic ACP–thioester intermediate. Co-crystal structures of this protein with palmitate or a bicyclic substrate mimic show that the PT domain is able to bind both linear and bicyclic compounds. The authors identify a large cyclization chamber and propose how the PT domain controls the specificity of the biosynthetic reactions that generate the intermediate that is eventually converted into aflatoxin B1.

Suggested Citation

  • Jason M. Crawford & Tyler P. Korman & Jason W. Labonte & Anna L. Vagstad & Eric A. Hill & Oliver Kamari-Bidkorpeh & Shiou-Chuan Tsai & Craig A. Townsend, 2009. "Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization," Nature, Nature, vol. 461(7267), pages 1139-1143, October.
    • Handle: RePEc:nat:nature:v:461:y:2009:i:7267:d:10.1038_nature08475
    DOI: 10.1038/nature08475
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