Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

Ronja Driller; Daniel Garbe; Norbert Mehlmer; Monika Fuchs; Keren Raz; Dan Thomas Major; Thomas Brück; Bernhard Loll

doi:10.3762/bjoc.15.228

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

Ronja Driller, Daniel Garbe, Norbert Mehlmer, Monika Fuchs, Keren Raz, Dan Thomas Major, Thomas Brück, Bernhard Loll

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2355-2368
Number of pages	14
Journal	Beilstein Journal of Organic Chemistry
Volume	15
DOIs	https://doi.org/10.3762/bjoc.15.228
State	Published - 2 Oct 2019

Bibliographical note

Publisher Copyright:
© 2019 Driller et al.; licensee Beilstein-Institut. License and terms: see end of document.

Funding

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.

Funders	Funder number
Werner Siemens-Stiftung
Bundesministerium für Bildung und Forschung	031A305A, 031A276A
Israel Science Foundation	1683/18, 2146/15
Bayerisches Staatsministerium für Wirtschaft, Infrastruktur, Verkehr und Technologie	1340/68351/13/2013

Keywords

Biotechnology
CotB2
Crystal structure
Cyclooctatin
Diterpene
Reaction mechanism
Terpene synthase

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10.3762/bjoc.15.228

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abstract = "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.",

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Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

Abstract

Bibliographical note

Funding

Keywords

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