The hedamycin locus implicates a novel aromatic PKS priming mechanism

Tsion Bililign, Chang Gu Hyun, Jessica S. Williams, Anne M. Czisny, Jon S. Thorson

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber. Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketide synthase (PKS) genes, and two putative C-glycosyltransferase genes. As the first report of the cloning of the biosynthetic gene cluster for the pluramycin antibiotics, this work suggests that the biosynthesis of pluramycins utilize an iterative type I PKS system for the generation of a novel starter unit that subsequently primes the type II PKS system. It also implicates the involvement of a second catalytic ketosynthase (KSIII) to regulate this unusual priming step. Gene disruption is used to confirm the importance of both type I and II PKS genes for the biosynthesis of hedamycin.

Original languageEnglish
Pages (from-to)959-969
Number of pages11
JournalChemistry and Biology
Volume11
Issue number7
DOIs
StatePublished - Jul 2004

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Institutes of Health (CA84374 and GM58196).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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