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Chembiochem. 2015 Jul 6;16(10):1443-7. doi: 10.1002/cbic.201500177. Epub 2015 May 15.

Salinipyrone and Pacificanone Are Biosynthetic By-products of the Rosamicin Polyketide Synthase.

Author information

  • 1Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA).
  • 2Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
  • 3Pediatrics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).
  • 4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA).
  • 5Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0204 (USA). bsmoore@ucsd.edu.
  • 6Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA). bsmoore@ucsd.edu.

Abstract

Salinipyrones and pacificanones are structurally related polyketides from Salinispora pacifica CNS-237 that are proposed to arise from the same modular polyketide synthase (PKS) assembly line. Genome sequencing revealed a large macrolide PKS gene cluster that codes for the biosynthesis of rosamicin A and a series of new macrolide antibiotics. Mutagenesis experiments unexpectedly correlated salinipyrone and pacificanone biosynthesis to the rosamicin octamodule Spr PKS. Remarkably, this bifurcated polyketide pathway illuminates a series of enzymatic domain- and module-skipping reactions that give rise to natural polyketide product diversity. Our findings enlarge the growing knowledge of polyketide biochemistry and illuminate potential challenges in PKS bioengineering.

KEYWORDS:

Salinispora; biosynthesis; macrolide antibiotics; polyketide synthases

PMID:
25930739
PMCID:
PMC4545249
DOI:
10.1002/cbic.201500177
[PubMed - indexed for MEDLINE]
Free PMC Article
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