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

12 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

Funding 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.

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

Keywords

Biotechnology
CotB2
Crystal structure
Cyclooctatin
Diterpene
Reaction mechanism
Terpene synthase

Access to Document

10.3762/bjoc.15.228

Cite this

@article{ae8bed1271ed4519bdee6214bd18d60c,

title = "Current understanding and biotechnological application of the bacterial diterpene synthase CotB2",

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.",

keywords = "Biotechnology, CotB2, Crystal structure, Cyclooctatin, Diterpene, Reaction mechanism, Terpene synthase",

author = "Ronja Driller and Daniel Garbe and Norbert Mehlmer and Monika Fuchs and Keren Raz and Major, {Dan Thomas} and Thomas Br{\"u}ck and Bernhard Loll",

note = "Publisher Copyright: {\textcopyright} 2019 Driller et al.; licensee Beilstein-Institut. License and terms: see end of document.",

year = "2019",

month = oct,

day = "2",

doi = "10.3762/bjoc.15.228",

language = "אנגלית",

volume = "15",

pages = "2355--2368",

journal = "Beilstein Journal of Organic Chemistry",

issn = "1860-5397",

publisher = "Beilstein-Institut Zur Forderung der Chemischen Wissenschaften",

}

TY - JOUR

T1 - Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

AU - Driller, Ronja

AU - Garbe, Daniel

AU - Mehlmer, Norbert

AU - Fuchs, Monika

AU - Raz, Keren

AU - Major, Dan Thomas

AU - Brück, Thomas

AU - Loll, Bernhard

PY - 2019/10/2

Y1 - 2019/10/2

N2 - 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.

AB - 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.

KW - Biotechnology

KW - CotB2

KW - Crystal structure

KW - Cyclooctatin

KW - Diterpene

KW - Reaction mechanism

KW - Terpene synthase

UR - http://www.scopus.com/inward/record.url?scp=85073110310&partnerID=8YFLogxK

U2 - 10.3762/bjoc.15.228

DO - 10.3762/bjoc.15.228

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31666870

AN - SCOPUS:85073110310

SN - 1860-5397

VL - 15

SP - 2355

EP - 2368

JO - Beilstein Journal of Organic Chemistry

JF - Beilstein Journal of Organic Chemistry

ER -

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this