Biosynthesis of the β-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring β-amino acyl-S-carrier protein intermediates

Steven G. Van Lanen, Pieter C. Dorrestein, Steve D. Christenson, Wen Liu, Jianhua Ju, Neil L. Kelleher, Ben Shen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The enediyne antitumor antibiotic C-1027 chromoprotein is produced by Streptomyces globisporus. The biosynthesis of the (S)-3-chloro-4,5-dihydroxy-β-phenylalanine moiety (boxed) of the C-1027 chromophore (1) from l-tyrosine (3) and its incorporation into 1 are catalyzed by six enzymes: SgcC, SgcC1, SgcC2, SgcC3, SgcC4, ShcC5. In vivo and in vitro characterization of these enzymes delineated this pathway, unveiling a novel strategy for β-amino acid modification featuring β-amino acyl-S-carrier protein intermediates. These findings shed new light into β-amino acid biosynthesis and present a new opportunity to engineer the C-1027 biosynthetic machinery for the production of novel analogues as exemplified by 20-deschloro-C-1027 (4), 20-deschro-22-deshydroxy-C-1027 (5), and 22-deshydroxy-C-1027 (6).

Original languageEnglish (US)
Pages (from-to)11594-11595
Number of pages2
JournalJournal of the American Chemical Society
Volume127
Issue number33
DOIs
StatePublished - Aug 24 2005

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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