Macroamidine formation in bottromycins is catalyzed by a divergent YcaO enzyme

Franz, L., Adam, S., Santos-Aberturas, J., Truman, A. W. and Koehnke, J. (2017) Macroamidine formation in bottromycins is catalyzed by a divergent YcaO enzyme. Journal of the American Chemical Society, 139(50), pp. 18158-18161. (doi: 10.1021/jacs.7b09898) (PMID:29206037)

Abstract

The YcaO superfamily of proteins catalyzes the phosphorylation of peptide backbone amide bonds, which leads to the formation of azolines and azoles in ribosomally synthesized and post-translationally modified peptides (RiPPs). Bottromycins are RiPPs with potent antimicrobial activity, and their biosynthetic pathway contains two divergent, stand-alone YcaO enzymes, IpoC and PurCD. From an untargeted metabolomics approach, it had been suggested that PurCD acts with a partner protein to form the 12-membered macroamidine unique to bottromycins. Here we report the biochemical characterization of IpoC and PurCD. We demonstrate that IpoC installs a cysteine-derived thiazoline, whereas PurCD alone is sufficient to create the macroamidine structure. Both enzymes are catalytically promiscuous, and we generated 10 different macroamidines. Our data provide important insights into the versatility of YcaO enzymes, their ability to utilize different nucleophiles and provide a framework for the creation of novel bottromycin derivatives with enhanced bioactivity.

• Item Type: Articles
• Additional Information: J.K. thanks the DFG for an Emmy Noether Fellowship (KO 4116/3-1). This work was also supported by BBSRC grant BB/ M003140/1 (A.W.T. and J.S.-A.) and a Royal Society University Research Fellowship (A.W.T.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Koehnke, Professor Jesko
• Authors: Franz, L., Adam, S., Santos-Aberturas, J., Truman, A. W., 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: 05 December 2017
• Copyright Holders: Copyright © 2017 American Chemcal Society
• First Published: First published in Journal of the American Chemical Society 139(50):18158-18161
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher