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Search for "CotB2" in Full Text gives 7 result(s) in Beilstein Journal of Organic Chemistry.
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme
Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144
- nature. To date, only five distinct FC-type DTSs, including fungi-derived PaFS/SdnA/MgMS and bacteria-derived CotB2/CpCS, have been reported (Figure 1) [20][21][22][23][24], implying that there still exists a large enzymatic space remaining to be explored. Herein, we characterize a two-gene cluster from
- ], MgMS [20], CotB2 [19], and CpCS [21] have been deciphered. All these enzymes undergo a common C1,11–C10,14-bicyclization to form a C15 carbocation, but differ a lot at the following C2,6 cyclization (Scheme 1B). CotB2 and CpCS trigger the C2,6 cyclization via a distant hydride shift, whereas PaFS
Understanding the role of active site residues in CotB2 catalysis using a cluster model
Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7
- , Dept. of Chemistry, Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany 10.3762/bjoc.16.7 Abstract Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of a large number of terpenes. CotB2 is a diterpene cyclase from Streptomyces
- melanosporofaciens, which catalyzes the formation of cycloocta-9-en-7-ol, a precursor to the next-generation anti-inflammatory drug cyclooctatin. In this work, we present evidence for the significant role of the active site's residues in CotB2 on the reaction energetics using quantum mechanical calculations in an
- active site cluster model. The results revealed the significant effect of the active site residues on the relative electronic energy of the intermediates and transition state structures with respect to gas phase data. A detailed understanding of the role of the enzyme environment on the CotB2 reaction
Current understanding and biotechnological application of the bacterial diterpene synthase CotB2
Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228
- , Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel 10.3762/bjoc.15.228 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
Phylogenomic analyses and distribution of terpene synthases among Streptomyces
Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115
- exceptions, S. rubrolavendulae MJM4426 and S. collinus Tü 365, members of the other two phylogenomic clades that also present a cyclooctat-9-en-7-ol synthase. Cyclooctat-9-en-7-ol synthase (CotB2) from S. melanosporofaciens was the first bacterial type I diterpene cyclase characterised [40] and its crystal
Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems
Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85
- insights into cyclization mechanism but also lead to novel products or changes in the product spectra. This has also been demonstrated for the bacterial diterpene cyclooctat-9-en-7-ol synthase (CotB2) [57], also a putative Class I TPS. Mutation of tryptophan 288 to glycine in CotB2 resulted in the
- stereoselective synthesis of (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, a bicyclic diterpene (Scheme 2). Dollabellanes derive mostly from marine organisms and display bioactivities such as antiviral and cytotoxic effects [59]. Dolabellatriene from a reprogrammed CotB2 contribute with antimicrobial activity
- inaccessible. A good example is the mutagenesis of the bacterial diterpene synthase CotB2 that resulted in dolabellatriene-type scaffolds, which were by then mostly found in marine organisms [59]. To that end, these new routes can provide substantial and environmentally friendly alternatives for sourcing
Recent highlights in biosynthesis research using stable isotopes
Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271
- melanosporofaciens [64]. The cyclization of geranylgeranyl diphosphate (GGPP, 44) to 52 features an unexpected carbon backbone rearrangement, which was shown recently by Kuzuyama and co-workers using isotopically labeled glucose in vivo and labeled GGPP in vitro [65]. The reaction is catalysed by the enzyme CotB2
- –carbon-bond rearrangement and several hydride shifts, which were confirmed with elegant labeling experiments using (9,9-2H2)GGPP (a), (10-2H)GGPP (b), and (8,8-2H2)GGPP (c) in incubation experiments with recombinant CotB2 (Scheme 9). A mechanism that is in line with all labeling experiments proceeds via
- from carbon numbers of GGPP (44). Proposed mechanism of the cyclooctat-9-en-7-ol (52) biosynthesis catalysed by CotB2. Annotated hydrogen atoms (a–c) were investigated by deuterium labeling. Asterisks are used to follow the rearrangement of C-8 and C-9 (carbon numbers as for GGPP). Cyclization
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