Control of beta-Branching in Kalimantacin Biosynthesis: Application of 13C NMR to Polyketide Programming

Research output: Contribution to journalArticle (Academic Journal)

Abstract

The presence of beta‐branches in the structure of polyketides that possess potent biological activity underpins their widespread importance. Kalimantacin is a polyketide antibiotic with selective activity against staphylococci and its biosynthesis involves the unprecedented incorporation of three different and sequential beta‐branching modifications. Here we use purified single and multi‐domain enzyme components of the kalimantacin biosynthetic machinery to address in vitro how the pattern of beta‐branching in kalimantacin is controlled. Robust discrimination of enzyme products required the development of a generalisable assay, taking advantage of direct observe 13C NMR of a single carbon‐13 label incorporated into key biosynthetic mimics combined with favourable dynamic properties of an acyl carrier protein. We report a previously unassigned modular enoyl‐CoA hydratase (mECH) domain and the assembly of enzyme constructs and cascades that are able to generate each specific b‐branch.
Original languageEnglish
Pages (from-to)12576-12580
Number of pages5
JournalAngewandte Chemie
Volume131
Issue number36
Early online date7 Aug 2019
DOIs
Publication statusPublished - 2 Sep 2019

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

Keywords

  • Enoyl-CoA Hydratase
  • beta-branching
  • Batumin
  • Kalimantacin
  • polyketide
  • Synthetic biology

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