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Advances in polyketide synthase structure and function

Academic Article
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Overview

authors

  • Van Lanen, S. G.
  • Shen, Ben

publication date

  • 2008

journal

  • Current Opinion in Drug Discovery & Development  Journal

abstract

  • Recent progress in the understanding of polyketide synthase (PKS) continues to fuel the growth of combinatorial biosynthesis for natural product structural diversity. The structural analysis of many components of PKS, in particular for the modular type I 6-deoxyerythronilide B synthase (DEBS) involved in erythromycin biosynthesis, has provided structural imperatives for the observed biochemistry of DEBS and has enabled the generation of a working structural model of the entire DEBS system. New functions for PKS domains continue to be defined, such as the general control nonderepressible 5 (GCN5) N-acyltransferase strategy for polyketide chain initiation and the true identity of the elusive precursor for the methoxymalonylate extender unit. Novel molecular architectures have been continuously uncovered, including the 'AT-less' PKS and enediyne PKS, thereby expanding the known bacterial PKS paradigms beyond the prototypical type I, II and III PKSs. Finally, the genetic characterization of PKS in vivo and biochemical studies of PKS in vitro have also been greatly facilitated by the application of emerging technologies, such as RNA-mediated gene silencing, reconstitution of an entire polyketide biosynthetic pathway in a model heterologous host and Fourier-transform mass spectroscopy. The application of these technologies is discussed.

subject areas

  • Animals
  • Biological Products
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Polyketide Synthases
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Research

keywords

  • 6-deoxyerythronolide B synthase
  • DEBS
  • enediynes
  • fatty acid synthase
  • natural product biosynthesis
  • polyketide synthase
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Identity

International Standard Serial Number (ISSN)

  • 1367-6733

PubMed ID

  • 18283606
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Additional Document Info

start page

  • 186

end page

  • 195

volume

  • 11

issue

  • 2

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