Characterization of the stereoselective P450 enzyme BotCYP enables the in vitro biosynthesis of the Bottromycin Core Scaffold

Adam, S., Franz, L., Milhim, M., Bernhardt, R., Kalinina, O. V. and Koehnke, J. (2020) Characterization of the stereoselective P450 enzyme BotCYP enables the in vitro biosynthesis of the Bottromycin Core Scaffold. Journal of the American Chemical Society, 142(49), pp. 20560-20565. (doi: 10.1021/jacs.0c10361)

Full text not currently available from Enlighten.

Abstract

Bottromycins are ribosomally synthesized and post-translationally modified peptide natural product antibiotics that are effective against high-priority human pathogens such as methicillin-resistant Staphylococcus aureus. The total synthesis of bottromycins involves at least 17 steps, with a poor overall yield. Here, we report the characterization of the cytochrome P450 enzyme BotCYP from a bottromycin biosynthetic gene cluster. We determined the structure of a close BotCYP homolog and used our data to conduct the first large-scale survey of P450 enzymes associated with RiPP biosynthetic gene clusters. We demonstrate that BotCYP converts a C-terminal thiazoline to a thiazole via an oxidative decarboxylation reaction and provides stereochemical resolution for the pathway. Our data enable the two-pot in vitro production of the bottromycin core scaffold and may allow the rapid generation of bottromycin analogues for compound development.

Item Type:Articles
Additional Information:Funding: J.K. thanks the German Research Foundation for an Emmy Noether Fellowship (KO 4116/3-2).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Koehnke, Dr Jesko
Authors: Adam, S., Franz, L., Milhim, M., Bernhardt, R., Kalinina, O. V., and Koehnke, J.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Journal of the American Chemical Society
Publisher:American Chemical Society
ISSN:0002-7863
ISSN (Online):1520-5126
Published Online:28 November 2020

University Staff: Request a correction | Enlighten Editors: Update this record