Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• replaced with Ala, the resulting variant F65A produced a novel 5/8/6/6 tetracyclic sesterterpene in the presence of 29 [28]. Domain swapping is another useful approach for changing the PTTS product profile. For example, EvVS from Emericella variecolor majorly produced diterpene variediene (34) with a minor

• production of sesterterpene (2E)-α-cericerene (33) in vitro (Figure 3a) [29]. By replacing the PT domain of EvVS with that of sester-TS EvSS, the resulting variant generated 33, which was not produced in vivo as the major product, both in vitro and in vivo. These studies revealed that altering and enhancing

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• phylogenetically related enzymes were in one case not expressed and in two cases inactive, suggesting pseudogenisation in the respective branch of the phylogenetic tree. Furthermore, a diterpene synthase for allokutznerene and a sesterterpene synthase for sesterviolene were identified. Keywords: actinomycetes

• bacterial terpene synthases have been identified [11], including enzymes for the non-canonical compounds geosmin (7) [12] and 2-methylisoborneol (8) [13]. Recent developments also revealed the presence of sesterterpene synthases in bacteria exemplified by the enzymes for sesterviridene (9) in Kitasatospora

• from the same branch from S. subrutilus, S. natalensis and S. violens were in one case not expressed and in two cases only yielded soluble, but inactive enzymes with any of the tested substrates GPP, FPP, GGPP and GFPP (Table 1, entries 11–13). Diterpene and sesterterpene synthases One more terpene

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• , including the monoterpene precursor geranyl diphosphate (GPP) [1], the precursor for sesquiterpenes farnesyl diphosphate (FPP) [2], geranylgeranyl diphosphate (GGPP) towards diterpenes [3], and the sesterterpene precursor geranylfarnesyl diphosphate (GFPP) [4]. It has been demonstrated recently, that even

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• Anwei Hou Jeroen S. Dickschat Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany 10.3762/bjoc.17.161 Abstract The sesterterpene synthase SmTS1 from Streptomyces mobaraensis contains several unusual residues in positions that

• , turning SmTS1 from a sesterterpene into a diterpene synthase. This article gives rational explanations for these findings that may generally allow for protein engineering of other terpene synthases to improve their catalytic efficiency or to change their functions. Keywords: biosynthesis; enzyme

• (GFPP, C25) for sesterterpene biosynthesis. Type I terpene synthases (TPSs) activate these acyclic molecules by the abstraction of diphosphate to produce a reactive allyl cation that can initiate a cascade reaction through typical carbocation chemistry, including cyclisation reactions by intramolecular

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• investigation of the electron impact mass spectrometry (EIMS) fragmentation reactions of these sesterterpene hydrocarbons. Keywords: isotopes; mass spectrometry; reaction mechanisms; sesterterpenes; Streptomyces mobaraensis; Introduction The sestermobaraenes A–F (1–6) and sestermobaraol (7) are a series of

• bacterial sesterterpenes that were recently discovered by us from the actinomycete Streptomyces mobaraensis through a genome mining approach (Figure 1) [1]. All seven compounds are produced by a canonical terpene synthase, representing the first reported sesterterpene synthase of the classical type I from

• synthase catalysed reactions into each single position of a terpene, which is useful for the deep investigations on mass spectrometric fragmentation reactions. The present study provides the first example for such investigations on sesterterpene fragmentations. The applied method, once the synthetic 13C

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• (Chromodorididae, Doridoidea) nudibranchs, their egg ribbons, and the associated dietary sponge Spongia cf. agaricina (Demospongiae, Porifera) led to the isolation of the structurally new scalarane-type sesterterpene 12-deacetoxy-4-demethyl-11,24-diacetoxy-3,4-methylenedeoxoscalarin, with an unprecedented position

• bacteria Arthrobacter crystallopoietes (DSM 20117) and Bacillus megaterium (DSM 32). Keywords: antibacterial; Dictyoceratida; Nudibranchia; scalarane; sesterterpene; Introduction In habitats with intense competition and feeding pressure, such as coral reefs, sessile or slow-moving organisms commonly

• , Demospongiae). We describe the structure elucidation of the new scalarane sesterterpene 12-deacetoxy-4-demethyl-11,24-diacetoxy-3,4-methylenedeoxoscalarin (Figure 2), isolated from all our Doriprismatica stellata nudibranch, egg ribbon and Spongia cf. agaricina samples (Figure 3). It is the first scalarane

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• biosynthetic gene cluster (tpc) for terpestacin (12) has been recently identified from Bipolaris maydis [36]. A didomain sesterterpene synthase (tpcA) with a terpene cyclase domain and polyprenyltransferase domain was demonstrated to be responsible for the production of the sesterterpene backbone of 12. A

• BLASTp search using tpcA as query against the genome of B. sorokiniana ND90Pr and BRIP10943 identified COCSADRAFT_342920 in ND90Pr (and its homolog in BRIP10943), which shares 96% identity to tpcA. In the vicinity of the sesterterpene synthase gene, we also identified homologs for the two P450 oxygenases

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• the first detailed analysis of the inherent atomic mobility in carbocation intermediates during sesterterpene biosynthesis. We identified two methyl groups as the least mobile of all the carbons of the carbocation intermediates in the first half of the cyclization cascade. Our analysis suggests that

• above-mentioned reports, we regard this as reasonable. Nevertheless, to minimize the effects of such changes, we focused on the first half of the cyclization cascade. In this study, we report the first analysis of the inherent structural mobility of carbocation intermediates in sesterterpene

• conformational preorganization [20] of GFPP bound to a sesterterpene synthase on the reaction outcome, we computed the inherent atomic mobility in the carbocation intermediates during the biosynthesis of two sesterterpenes, quiannulatene and sesterfisherol. Two methyl groups, i.e., C20 and C23, remain static

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• synthase into a sesterterpene synthase by interchanging the prenyltransferase domain. Combining these structural insights and newly created biosynthetic routes with functional expression in bacterial production hosts, industrial scale synthesis of fragrance compound (+)-sclareol, (13R)-(+)-manoyl oxide

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• sesterfisherol (59, Scheme 10), the product of a bifunctional sesterterpene cyclase (C25) from Neosartorya fischeri [69]. In this case, [1-13C,2H3]acetate was fed and the resulting labeling pattern of an epoxidation product was analyzed by 13C NMR, revealing a loss of deuterium from carbons C-2, C-6 and C-10 by

• the tertiary cation 57 by two sequential 1,2-hydride shifts and another cyclization. Two 1,2-hydride shifts yield the allylic cation 58, which is finally quenched by water to the sesterterpene product 59. The involved 1,2-hydride shifts along this pathway explain the missing upfield-shifted 13C

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. Keywords: aldol reaction; astakolactin; lactonization; MNBA; terpenoids; Introduction

• Astakolactin (1) is a novel sesterterpene metabolite [1][2][3][4][5] first reported in 2003 by Roussis et al [6]. It was isolated from the marine sponge Cacospongia scalaris, which was collected from the gulf of Astakos in the Ionian Sea near Greece. The structure proposed for compound 1 is a bicyclic linear