These authors contributed equally to this work.
Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis†
Article first published online: 6 APR 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 53, Issue 19, pages 4840–4844, May 5, 2014
How to Cite
Zhang, G., Zhang, W., Zhang, Q., Shi, T., Ma, L., Zhu, Y., Li, S., Zhang, H., Zhao, Y.-L., Shi, R. and Zhang, C. (2014), Mechanistic Insights into Polycycle Formation by Reductive Cyclization in Ikarugamycin Biosynthesis. Angew. Chem. Int. Ed., 53: 4840–4844. doi: 10.1002/anie.201402078
We thank Prof. Hanjie Ying in Nanjing University of Technology for providing the plasmid pRSF-BmGDH and Prof. Lichuan Gu in Shandong University for providing the strain Thermoplasma acidophilum ATCC 25905. We thank Professors Shuangjun Lin (Shanghai Jiao Tong University) and Ang Li (Shanghai Institute of Organic Chemistry) for helpful discussions. This work is supported in part by the National Natural Science Foundation of China (grant numbers 31125001 and 21377085), the Ministry of Science and Technology of China (grant numbers 2010CB833805 and 2012AA092104), the Chinese Academy of Sciences (grant numberXDA11030403), and the Administration of Ocean and Fisheries of Guangdong Province (grant numbers GD2012-D01-001 and GD2012-D01-002). We are grateful for recording spectroscopic data at SCSIO.
- Issue published online: 2 MAY 2014
- Article first published online: 6 APR 2014
- Manuscript Received: 4 FEB 2014
- National Natural Science Foundation of China. Grant Numbers: 31125001, 21377085
- Ministry of Science and Technology of China. Grant Numbers: 2010CB833805, 2012AA092104
- Chinese Academy of Sciences. Grant Number: XDA11030403
- Administration of Ocean and Fisheries of Guangdong Province. Grant Numbers: GD2012-D01-001, GD2012-D01-002
- heterologous expression;
- polycyclic tetramate macrolactams;
- reductive cyclization
Ikarugamycin is a member of the polycyclic tetramate macrolactams (PTMs) family of natural products with diverse biological activities. The biochemical mechanisms for the formation of polycyclic ring systems in PTMs remain elusive. The enzymatic mechanism of constructing an inner five-membered ring in ikarugamycin is reported. A three-gene-cassette ikaABC from the marine-derived Streptomyces sp. ZJ306 is sufficient for conferring ikarugamycin production in a heterologous host. IkaC catalyzes a reductive cyclization reaction to form the inner five-membered ring by a Michael addition-like reaction. This study provides the first biochemical evidence for polycycle formation in PTMs and suggests a reductive cyclization strategy which may be potentially applicable in general to the corresponding ring formation in other PTMs.