An ATP-independent strategy for amide bond formation in antibiotic biosynthesis

Masanori Funabashi, Zhaoyong Yang, Koichi Nonaka, Masahiko Hosobuchi, Yoko Fujita, Tomoyuki Shibata, Xiuling Chi, Steven G. Van Lanen

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

A-503083 B, a capuramycin-type antibiotic, contains an L-aminocaprolactam and an unsaturated hexuronic acid that are linked via an amide bond. A putative class C β-lactamase (CapW) was identified within the biosynthetic gene cluster that-in contrast to the expected β-lactamase activity-catalyzed an amide-ester exchange reaction to eliminate the L-aminocaprolactam with concomitant generation of a small but significant amount of the glyceryl ester derivative of A-503083 B, suggesting a potential role for an ester intermediate in the biosynthesis of capuramycins. A carboxyl methyltransferase, CapS, was subsequently demonstrated to function as an S-adenosylmethionine-dependent carboxyl methyltransferase to form the methyl ester derivative of A-503083 B. In the presence of free L-aminocaprolactam, CapW efficiently converts the methyl ester to A-503083 B, thereby generating a new amide bond. This ATP-independent amide bond formation using methyl esterification followed by an ester-amide exchange reaction represents an alternative to known strategies of amide bond formation. 93616625 93616626 93616627 93616628 93616629 93616630

Original languageEnglish
Pages (from-to)581-586
Number of pages6
JournalNature Chemical Biology
Volume6
Issue number8
DOIs
StatePublished - Aug 2010

Bibliographical note

Funding Information:
This work is supported in part by the Kentucky Science and Technology Corporation (S.V.L.). We thank G. Elliott and J. Jacobsen (Univ. Kentucky) for technical assistance in mass and NMR spectroscopy.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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