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

Lookup NU author(s): Professor Paul RaceORCiD

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Abstract

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. The presence of β-branches in the structure of polyketides that possess potent biological activity underpins the widespread importance of this structural feature. Kalimantacin is a polyketide antibiotic with selective activity against staphylococci, and its biosynthesis involves the unprecedented incorporation of three different and sequential β-branching modifications. We use purified single and multi-domain enzyme components of the kalimantacin biosynthetic machinery to address in vitro how the pattern of β-branching in kalimantacin is controlled. Robust discrimination of enzyme products required the development of a generalisable assay that takes advantage of 13C NMR of a single 13C 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 β-branch.

Publication metadata

Author(s): Walker PD, Williams C, Weir ANM, Wang L, Crosby J, Race PR, Simpson TJ, Willis CL, Crump MP

Publication type: Article

Publication status: Published

Journal: Angewandte Chemie - International Edition

Year: 2019

Volume: 58

Issue: 36

Pages: 12446-12450

Print publication date: 02/09/2019

Online publication date: 11/07/2019

Acceptance date: 11/07/2019

ISSN (print): 1433-7851

ISSN (electronic): 1521-3773

Publisher: Wiley-VCH Verlag

URL: https://doi.org/10.1002/anie.201905482

DOI: 10.1002/anie.201905482

PubMed id: 31294525

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