Thioholgamides: thioamide-containing cytotoxic RiPP natural products

Kjaerulff, L., Sikandar, A., Zaburannyi, N., Adam, S., Herrmann, J., Koehnke, J. and Müller, R. (2017) Thioholgamides: thioamide-containing cytotoxic RiPP natural products. ACS Chemical Biology, 12(11), pp. 2837-2841. (doi: 10.1021/acschembio.7b00676) (PMID:28981254)

Abstract

Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC50 of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.

• Item Type: Articles
• Additional Information: R. Müller would like to acknowledge funding from DFG Forschergruppe FOR 1406. J. Koehnke would like to thank the Deutsche Forschungsgemeinschaft for an Emmy Noether fellowship (KO4116/3-1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Koehnke, Professor Jesko
• Authors: Kjaerulff, L., Sikandar, A., Zaburannyi, N., Adam, S., Herrmann, J., Koehnke, J., and Müller, R.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: ACS Chemical Biology
• Publisher: American Chemical Society
• ISSN: 1554-8929
• ISSN (Online): 1554-8937
• Published Online: 17 October 2017
• Copyright Holders: Copyright © 2017 American Chemcal Society
• First Published: First published in ACS Chemical Biology 12(11):2837-2841
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher