CotB2 catalyzes the first committed step in cyclooctatin biosynthesis of the soil bacterium Streptomyces melanosporofaciens. To date, CotB2 represents the best studied bacterial diterpene synthase. Its reaction mechanism has been addressed by isoptope labeling, targeted mutagenesis and theoretical computations in the gas phase, as well as full enzyme molecular dynamic simulations. By X-ray crystallography different snapshots of CotB2 from the open, inactive, to the closed, active conformation have been obtained in great detail, allowing us to draw detailed conclusions regarding the catalytic mechanism at the molecular level. Moreover, numerous alternative geranylgeranyl diphosphate cyclization products obtained by CotB2 mutagenesis have exciting applications for the sustainable production of high value bioactive substances.
|Number of pages||14|
|Journal||Beilstein Journal of Organic Chemistry|
|State||Published - 2 Oct 2019|
Bibliographical noteFunding Information:
R. Driller was supported by Elsa-Neumann and Nüsslein-Volhard stipends. D. T. Major acknowledges support from the Israel Science Foundation (Grant #2146/15 and 1683/18). T. Brück gratefully acknowledges funding by the Werner Siemens foundation for establishing the field of Synthetic Biotechnology at the Technical University of Munich (TUM). Additionally, the German Federal Ministry of Education and Research supported TB and DG through the project OMCBP (Grant #031A276A), while TB and MF were supported by the project SysBioTerp (Grant #031A305A). Furthermore, TB and NM acknowledge funding by the Bavarian Ministry of Economic Affairs, Regional Development and Energy for the bioinsecticide project (Grant #1340/68351/13/2013). We are grateful to M. Wahl for continuous encouragement and support.
© 2019 Driller et al.; licensee Beilstein-Institut. License and terms: see end of document.
- Crystal structure
- Reaction mechanism
- Terpene synthase