Functional analyses of oxygenases in jadomycin biosynthesis and identification of JadH as a bifunctional oxygenase/dehydrase

Yi Hua Chen, Chen Chen Wang, Lisa Greenwell, Uwe Rix, Dirk Hoffmeister, Leo C. Vining, Jürgen Rohr, Ke Qian Yang

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

A novel angucycline metabolite, 2,3-dehydro-UWM6, was identified in ajadH mutant of Streptomyces venezuelae ISP5230. Both UWM6 and 2,3-dehydro-UWM6 could be converted to jadomycin A or B by a ketosynthase α (jadA) mutant of S. venezuelae. These angucycline intermediates were also converted to jadomycin A by transformant of the heterologous host Streptomyces lividans expressing the jadFGH oxygenases in vivo and by its cell-free extracts in vitro; thus the three gene products JadFGH are implicated in catalysis of the postpolyketide synthase biosynthetic reactions converting UWM6 to jadomycin aglycone. Genetic and biochemical analyses indicate that JadH possesses dehydrase activity, not previously associated with polyketide-modifying oxygenase. Since the formation of aromatic polyketides often requires multiple dehydration steps, bifunctionality of oxygenases modifying aromatic polyketides may be a general phenomenon.

Original languageEnglish
Pages (from-to)22508-22514
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number23
DOIs
StatePublished - Jun 10 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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