Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

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

• comprise the largest and structurally most diverse family of natural products, currently representing over 80,000 reported structures from all kingdoms of life [3]. The largest diversity of terpenoids is reported for the plant kingdom where higher terpenes represent secondary metabolic products, which are

• ]. Theoretical quantum mechanical (QM) investigations on the chemistry of terpenes in the gas phase have provided a detailed understanding of the carbocation mechanisms underlying terpene synthase function [25][26][27]. Further, we have used multiscale modeling tools to study the effects of the enzyme

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• Jeroen S. Dickschat Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Straße 1, D-53121 Bonn, Germany 10.3762/bjoc.15.292 Keywords: Terpenes; With more than 80,000 known compounds terpenes represent the largest class of natural

• elucidation, total synthesis, biosynthetic studies, bioactivity and functionalisation for mode of action studies, and other applications of terpenes, e.g. as fragrances. I thank all colleagues who have participated in this issue for their contributions and the whole Beilstein team for the professional support

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• rearrangements, creating the basic hydrocarbon skeleton of a terpene [10][11]. This basic hydrocarbon skeleton is then modified to generate a large number of terpenoid structures, which can be further modified by addition of other building blocks, like sugars, amino acids, or fatty acids [12]. Terpenes are named

• . Review Remaining challenges in terpene (bio)synthesis While the large number of characterized terpenes and their biological and medical significance would suggest that there are good tools for terpene synthesis along with a good understanding of terpene biosynthesis, significant gaps in both remain

• -synthesis from biotechnologically produced taxol precursors [21], but a completely engineered pathway could provide a more efficient solution to taxol and specific analogs. There are additional puzzles about terpene biosynthesis that engineered pathways could address. As many other terpenes, 1 is produced

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• synthases (TPSs) are pivotal enzymes for the production of diverse terpenes, including monoterpenes, sesquiterpenes, and diterpenes. In our recent studies, dictyostelid social amoebae, also known as cellular slime molds, were found to contain TPS genes for making volatile terpenes. For comparison, here we

• (TPSs) catalyze the conversion of prenyl diphosphates to diverse terpenes [13]. Because all living organisms produce prenyl diphosphates, whether an organism has the ability to produce terpenes depends on whether it contains TPS genes. Recently we could show that dictyostelid social amoebae contain TPS

• . At the 18th day after the transfer, essentially the same profile of volatiles was detected (Figure 1A). Four terpene synthase genes were identified in P. polycephalum With the identification of terpenes from the headspace of P. polycephalum (Figure 1), the next question was how they are synthesized

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• : Aspergillus; biosynthesis; drimane; secondary metabolites; sesquiterpenoid; terpenes; Introduction The fungal genus Aspergillus is well recognised as a source of structurally diverse terpenoids comprising monoterpenoids [1], sesquiterpenoids [2][3][4][5], diterpenoids [6], sesterterpenoids [7][8][9

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• Alexey Stepanyuk Andreas Kirschning Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.15.252 Abstract The history of fragrances is closely associated with the chemistry of terpenes

• and terpenoids. For thousands of years mankind mainly used plant extracts to collect ingredients for the creation of perfumes. Many of these extracts contain complex mixtures of terpenes, that show distinct olfactoric properties as pure compounds. When organic synthesis appeared on the scene, the

• number of perfumes with varying percentages and is the first example being used as a pure fragrance. Structurally, it is related to natural terpenes like many other synthetic fragrances. And indeed, the story began with a classic in the field of fragrances, the natural product ionone. Keywords

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 and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• mutagenesis have exciting applications for the sustainable production of high value bioactive substances. Keywords: biotechnology; CotB2; crystal structure; cyclooctatin; diterpene; reaction mechanism; terpene synthase; Introduction Terpenes represent one of the most diverse groups of natural biomolecules

• description of the bacterial TPS CotB2, we will therefore refer to the NSE motif only. Using host microorganisms, such as bacteria or baker’s yeast for the heterologous synthesis of terpenes increases the sustainability of bioactive terpene production by saving resources, as the production host can be fed

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• of them being the marine-adapted fungal strain Heydenia cf. alpina. The latter produced two new terpenoids, which are the first secondary metabolites from this genus. Keywords: FIND; fungal one-step isolation device; Heydenia cf. alpina; natural products; terpenes; Introduction Natural products

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• . viride to date. Keywords: genome mining; metabolic engineering; natural products; sesquiterpene synthase; terpenes; Trichoderma viride J1-030; Introduction Terpenoids represent the most diverse group of natural products, with a wide distribution in microorganisms, plants, insects and various marine

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

• germination. The putative biosynthetic relationships between the isolated sesquiterpenoids were also explored. Keywords: Bipolaris sorokiniana; phytotoxicity; sesquiterpenes; terpenes; Introduction Fungi belonging to the genus Bipolaris (teleomorph: Cochliobolus) have been reported to produce a diverse

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• , the trans-decalin scaffold is the ideal objective of numerous methodology studies. Inspired by nature’s highly efficient and stereochemically controlled syntheses of terpenes, up to now, various synthetic strategies to trans-decalin have been developed, e.g., Brønsted acid or Lewis acid-mediated

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• -copaene, β-copaene, α-cubebene, β-cubebene and the bicyclic δ-cadinene were biosynthesized via (S)-(−)-germacrene D rather than via (R)-(+)-germacrene D as intermediate. Keywords: biosynthesis; deuterium labeling; germacrene; HS-SPME; terpenes; TOF–MS; Introduction The aroma profile of grape berries at

• the time of physiological ripening is very complex and significantly influenced by potent flavoring substances of isoprenoid origin like mono- and sesquiterpenes [1][2]. Sesquiterpenes form a structurally diverse subgroup of terpenes consisting of three isoprene units [3]. Since the bicyclic

• )-(+)-germacrene D, that includes two consecutive 1,2-hydride shifts [33]. In all terpenes in Scheme 3, TOF–EIMS measurements showed that a deuterium atom is located in the isopropyl group. This can be explained by the assumption that in Vitis vinifera L. all sesquiterpenes are formed via the (S)-germacradienyl

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• for structural enlargement and at least one stereogenic center which is usually transferred into the final product. To assure the highest possible enantiomeric purity chirons are obtained in most instances from natural products like carbohydrates, amino acids, hydroxy acids or terpenes. The

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• analysis of this genus is discussed. Keywords: biosynthesis; evolution; geosmin; Streptomyces; terpenes; Introduction Streptomyces are soil bacteria that belong to the order of actinomycetales and are a rich source of natural products with broad biotechnological interest. Species of this genus have a

• revealed that terpenoids can be produced by all kingdoms of life including bacteria, fungi and protists [6][7][8][9][10]. The ability of an organism to produce terpenoids relies on whether the organism contains terpene synthase genes. Biosynthetically, the production of the different types of terpenes

• depends on the precursors that these synthases can accommodate: geranyl diphosphate (monoterpenes, C10), farnesyl diphosphate (sesquiterpenes, C15) and geranylgeranyl diphosphate (diterpenes, C20). The biological function of terpenes is best studied for plants where they play important roles in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• . In vitro studies showed not only a high promiscuity with respect to its numerous sesquiterpene products, including the structurally demanding terpenes longicyclene, longifolene and α-longipinene, but also to its substrates, as additional activity was observed with geranyl- and geranylgeranyl

• potential was also exploited in the preparation of sesquiterpene isotopomers, which provided insights into their EIMS fragmentation mechanisms. Keywords: enzyme mechanisms; isotopes; mass spectrometry; promiscuity; terpenes; Introduction The organic chemist usually prefers to work with pure compounds

• products, including structurally demanding polycyclic terpenes, HcS also served as a platform for investigating selected aspects of their EIMS fragmentation mechanisms. The labelling experiments performed with HcS described in this study therefore represent an encouragement to experimentally explore and

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• clusters. Keywords: bioinformatics; gene cluster analysis; natural products; secondary metabolites; structure elucidation; terpenes; Introduction The basidiomycete Agrocybe aegerita (synonym: A. cylindracea) was traditionally accommodated in the genus Agrocybe (family Bolbitiaceae) until a recent

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• ; metathesis; Michael addition; organocatalysis; terpenes; Introduction The guaiane sesquiterpene (−)-isoguaiene (1) has been isolated from the liverworts Pellia epiphylla [1] and Dumortiera hirsuta [2] as well as from several Pimpinella species [3][4], while the (+)-enantiomer of 1 has been isolated from the

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• ; carbocation chemistry; enzyme mechanisms; nerolidyl diphosphate; terpenes; Introduction Given the enormous impact of chirality within biomolecules for all forms of life, it is fascinating to see how nature is able to maintain and reproduce stereochemical information. This concept largely involves the

• transformations are ubiquitous, which diminishes the hard border between achiral and chiral. One intriguing example for this kind of reactivity is represented by terpene synthases (TSs), arguably building up the class of natural products with the highest density of stereochemical information, the terpenes. By

• still present. In this group, there are acyclic compounds like the linear sesquiterpene (E)-β-farnesene (1, Figure 1), which is known as an alarm pheromone in aphids [4][5], but also monocyclic terpenes like α-humulene (2), a widely occurring sesquiterpene in many essential oils [6][7]. Whereas the

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• extensive spectroscopic analysis and by comparison with the previously reported analogues. In a bioassay, compounds 1, 2 and 4 exhibited interesting inhibitory activities in vitro against PTP1B and NF-κB. Keywords: Clavularia viridis; Lemnalia flava; NF-κB; PTP1B; sesquiterpenoid; soft coral, terpenes

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• the charcoal filter traps were removed and extracted with CH2Cl2, followed by GC–MS analysis of the obtained extracts. For both strains a large number of compounds from different compound classes including alcohols, ketones, esters, terpenes and pyrazines were identified. Besides the observed minor

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• Abstract The volatiles emitted by agar plate cultures of three genome sequenced fungal strains from the genus Aspergillus were analysed by GC–MS. All three strains produced terpenes for which a biosynthetic relationship is discussed. The obtained data were also correlated to genetic information about the

• encoded terpene synthases for each strain. Besides terpenes, a series of aromatic compounds and volatiles derived from fatty acid and branched amino acid metabolism were identified. Some of these compounds have not been described as fungal metabolites before. For the compound ethyl (E)-hept-4-enoate known

• from cantaloupe a structural revision to the Z stereoisomer is proposed. Ethyl (Z)-hept-4-enoate also occurs in Aspergillus clavatus and was identified by synthesis of an authentic standard. Keywords: Aspergillus; GC–MS; genomics; terpenes; volatiles; Introduction Ascomycete fungi are a highly

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• different compound classes including fatty acid derivatives and polyketides, aromatic compounds, terpenes, sulfur and nitrogen compounds, and halogenated compounds is produced by ascomycete fungi [1]. Possibly the most widespread volatile secondary metabolite from fungi is (R)-oct-1-en-3-ol (1, Scheme 1), a

• biocontrol agents [6]. On the contrary, fungi can also produce mycotoxins, which must be excluded for their safe usage in agricultural biocontrol. Some volatiles, especially terpenes, point to the production of certain toxins in fungi, e.g., aristolochene (3) is the precursor of PR toxin in Penicillium

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• Biology, Hans Knöll Institute, Beutenbergstr. 11a, 07745 Jena, Germany 10.3762/bjoc.13.242 Abstract The genome of the predatory bacterium Herpetosiphon aurantiacus 114-95T harbors a number of biosynthesis genes, including four terpene cyclase genes. To identify the terpenes biosynthesized from H

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• stable elemanolide that is even more stable than its (Z,E)-germacrane. Keywords: biogenesis; density functional theory; reaction mechanism; sigmatropic rearrangement; terpenes; Introduction Germacranes are biogenetic precursors of elemanes [1][2][3][4], because germacranes can be easily transformed