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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)12446-12450
Number of pages5
JournalAngewandte Chemie
Volume58
Issue number36
Early online date7 Aug 2019
DOIs
DateAccepted/In press - 11 Jul 2019
DateE-pub ahead of print - 7 Aug 2019
DatePublished (current) - 28 Aug 2019

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.

    Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

    Research areas

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

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://doi.org/10.1002/anie.201905482 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 3 MB, PDF document

    Embargo ends: 7/08/20

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    Licence: Other

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