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Publication - Professor Matthew Crump

    Control of beta-Branching in Kalimantacin Biosynthesis

    Application of Direct Observe 13C NMR to Polyketide Programming.

    Citation

    Walker, P, Williams, C, Weir, A, Wang, L, Crosby, J, Race, P, Simpson, T, Willis, C & Crump, M, 2019, ‘Control of beta-Branching in Kalimantacin Biosynthesis: Application of Direct Observe 13C NMR to Polyketide Programming.’. Angewandte Chemie, vol 58., pp. 12446-12450

    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.

    Full details in the University publications repository