Control of β‐Branching in Kalimantacin Biosynthesis: Application of13C NMR to Polyketide Programming
| Autor: | John Crosby, Luoyi Wang, Thomas J. Simpson, Angus N M Weir, Christopher Williams, Paul R. Race, Paul D. Walker, Christine L. Willis, Matthew P. Crump |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Batumin
BrisSynBio 010402 general chemistry 01 natural sciences Catalysis BCS and TECS CDTs Polyketide Synthetic biology chemistry.chemical_compound polyketide Biosynthesis Enoyl-CoA Hydratase chemistry.chemical_classification biology beta-branching 010405 organic chemistry Bristol BioDesign Institute Kalimantacin Biological activity General Medicine Nuclear magnetic resonance spectroscopy General Chemistry Enoyl-CoA hydratase 0104 chemical sciences Acyl carrier protein Enzyme chemistry Biochemistry biology.protein |
| Zdroj: | 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 13C NMR to Polyketide Programming ', Angewandte Chemie, vol. 131, no. 36, pp. 12576-12580 . https://doi.org/10.1002/ange.201905482 |
| ISSN: | 1521-3773 1433-7851 |
| DOI: | 10.1002/anie.201905482 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text