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)
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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 |
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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, Professor 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 |
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