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

• synthases in Trichoderma viride have been seldom studied, despite the efficiency of filamentous fungi for terpenoid production. Using the farnesyl diphosphate-overexpressing Saccharomyces cerevisiae platform to produce diverse terpenoids, we herein identified an unknown sesquiterpene synthase from T. viride

• ], generating diverse complex structures and several bioactive products (e.g., 6α,9α,15-trihydroxycadinan-4-en-3-one, (+)-3,11,12-trihydroxycalamenene, and (−)-3,10,11,12-tetrahydroxycalamenene) [18]. Filamentous fungi are powerful producers of terpenoid products [19]. Many terpenoids produced by these fungi

• terpenoids have rarely been studied and the low concentrations of products under natural conditions have limited the pace of research in this field. Metabolic engineering makes the overproduction of different terpenoids from T. viride possible [21][24]. To increase the discovery efficiency of terpenoid

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

• responsible for production of 12. We are currently investigating the genetic basis for the biosynthesis of the sativene-type terpenoid compounds identified from B. sorokiniana. Conclusion Following the first and only reported isolation of a sativene-type sesquiterpenoid, sorokinianin (11), from B. sorokiniana

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• ]. The prenyl acceptors, HU and HA, were both surrounded by hydrophobic amino acids, including A44, A102, W117, L119, L259, V284, F288, and M291 [14], and the position of HU was additionally stabilized by hydrogen bonding between the N-1 of HU and E207 (Figure 5A). Remarkably, the terpenoid moieties of

• HU and HA were located at the same position, but their orientations were completely different. These data indicated that the hydrophobic interaction between the enzyme and the terpenoid moiety is important to support the prenyl acceptor, and the orientation can be altered dependently on their steric

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

• enzymatic step [1][2][3]. With this approach, nature makes perfect use of the versatile chemistry of carbocations with its hydride or proton shifts and Wagner–Meerwein rearrangements leading to a large variety of possible structures. Among terpenoid natural products, achiral compounds are rarely found, but

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

• indicated the existence of a trisubstituted double bond. All the above evidence suggested the laurane nature of this molecule, and literature research revealed that 1 should be an isomer of a known laurane-type terpenoid bromolaurenisol (1a) [16][17] due to their extremely similar NMR data and the same

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• terpenoid natural products containing the 1,4-dialdehyde moiety have been isolated from sources such as fungi, algae, sponges and molluscs [1]. Many of these natural products exhibit biological activity, ranging from anti-inflammatory to antimicrobial and antifeedant activities [1]. The prototypical

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• added to the suspension of the terpenoid and PIFA at 0 °C. In this manner, good to excellent yields (57–84%) were obtained for the formation of Z-derivative 3b, alcohol 3c [16], tosylamine 3d and diene 3e (Scheme 3). Once again, the selectivity is excellent as no reactions with the other double bonds or

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

• natural product discovery. By comparing the ion chromatograms of cultures that were grown in the presence or absence of singly labeled glucose, it might be possible to identify terpenoid natural products in a complex metabolic background. To validate the feasibility of this approach, we chose the

• . aurantiacus 114-95T features four genes coding for putative terpene cyclases, i.e., Haur_2145, Haur_2987, Haur_2988, and Haur_4149. While the class II cyclase Haur_2145 had already been associated with the production of the terpenoid O-methylkolavelool [17], the products of the other three enzymes have not

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• structures that can be further transformed into interesting potential biologically active heterocyclic derivatives such as terpenoid pyranes, lactones, (hydro)chromenes or pyridines, among others [23][24][25][26]. Depending on the connection of the two isoprene units, four different kinds of dimers can be

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• recombinant enzyme from C. pinensis, showing no formation of monoterpenes from GPP (A) and no formation of sesquiterpenes from FPP (B), but formation of a single diterpene alcohol 3 from GGPP (C) with the mass spectrum depicted in (D). Asterisks indicate non-terpenoid contaminants such as plasticisers

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

• natural products has been accomplished with industrially relevant production titers [75][76][77]. However, at present there is no clear preference for one microbial production host as each engineering endeavor requires a de novo benchmarking for a specific terpenoid product, indicating that even minimal

• -pinene or limonene [78]. At present, 27.4 g/L of amorphadiene is the highest published titer for any reported terpenoid produced in E. coli. This result is of particular industrial relevance as amorphadiene constitutes the sesquiterpenoid scaffold of the antimalarial drug artemisinin [79]. In comparison

• for highest yield of plasmid systems generally precedes genomic integration; 5: Isoprenoid precursor supply: precursor flux has to be balanced carefully to avoid metabolic overload and accumulation of unwanted byproducts; 6: Downstream terpenoid biosynthesis using heterologous enzymes; 7: Upscaling of

Lipids: fatty acids and derivatives, polyketides and isoprenoids

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2017, 13, 793–794, doi:10.3762/bjoc.13.78

• biosynthetically related polyketide pathways, and terpenoid biosynthesis. I hope that the present Thematic Series of the Beilstein Journal of Organic Chemistry on the interdisciplinary topic of “Lipids” will cover many topics of high interest to readers from chemistry, biochemistry, biophysics, medicine, pharmacy

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• -Ossietzki University Oldenburg, Schleusenstraße 1, 26382 Wilhelmshaven, Germany Zoologisches Forschungsmuseum Alexander Koenig, Adenauerallee 160, 53113 Bonn, Germany 10.3762/bjoc.13.50 Abstract Phyllodesmium longicirrum is the largest aeolidoidean species known to date, and extremely rich in terpenoid

• octocorallian food also offers a wide spectrum of terpenoid chemistry, which is incorporated and stored by Phyllodesmium. Only few chemical investigations were undertaken on Phyllodesmium species [10][11][12][13][14][15], describing mostly terpenoid secondary metabolites. Indirect evidence suggests that these

• against omnivorous fish, it is possible that some of the numerous secondary metabolites found in this study could be useful against a wider range of predators. In summary, chemical investigation of a single large P. longicirrum specimen resulted in isolation of 19 secondary metabolites of terpenoid origin

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• methodology in the total synthesis of aplysiallene [127], and more recently to bovidic acid [128] and cyclocapitelline [129]. Oxidative cyclizations in the synthesis of terpenoid natural products Linalool oxide The monoterpenoid trans-(+)-linalool oxide (79), containing a 2,2,5-trisubstituted THF ring, can be

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• -date-explored members of these halophilic or halotolerant myxobacteria are all grouped into the suborder Nannocystineae. Few of them were chemically investigated revealing around 11 structural types belonging to the polyketide, non-ribosomal peptide, hybrids thereof or terpenoid class of secondary

• date, five structures of putative polyketide, shikimate and terpenoid origin have been described and classified as salimabromide (26, Figure 12) [58], produced by E. salina SWB007, enhygrolides 27 and 28 and salimyxins 29 and 30 produced by E. salina SWB005 [60]. Salimabromide (26) is particularly

Natural products in synthesis and biosynthesis II

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 413–414, doi:10.3762/bjoc.12.44

• Sciences) for the discovery of the terpenoid antimalaria drug artemisinin that is produced by the plant Artemisia annua [3], and to Satoshi Õmura and William C. Campbell for the discovery of avermectins isolated from the actinobacterium Streptomyces avermitilis at the famous Kitasato Institute and for the

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• constitute a unique group of terpenoid bisindole natural products [1] sharing a linear cyclopenta[f]indole tricyclic partial structure. The cyclopenta[f]indole system also occurs as partial structure of the nodulisporic acids [2], the shearinines [3][4][5][6] and janthitrems [7][8][9][10]. While work has

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• terpenoid derived amines, menthylamine and its 8-substituted derivatives 1 represent a particularly interesting candidate. Due to the strong steric influence in the vicinity of the amino functionality, high selectivity can be expected for asymmetric transformations [26][27], since appropriate moieties as

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• classified taking into account the terpenoid structure (mono- and sesquiterpenoid hydrocarbons (M and S), oxygenated mono- and sesquiterpenes (OM and OS), as well as the cycle numbers (1/2/3/4 included in the sample code), which indicates the structure rigidity/flexibility). The PCA variables are the

• variables. The O. basilicum L. essential oil components were encoded, according to the terpenoid classification, as monoterpenoid hydrocarbons (M), oxygenated monoterpenes (OM), sesquiterpenoid hydrocarbons (S), and oxygenated sesquiterpenes (OS). Furthermore, the number of cyclic moieties in the terpenoid

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• phytopathogenic fungus Sphaeropsis sapinea, displaying anti-gram-positive bacterial, antiviral, antiprotozoal and phytotoxic activity [10][11][12]. We further focused on the fractionation containing the minor terpenoid constituents with characteristic signals for terminal vinyl group detected by 1H NMR from the

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• terpenoid elements designed to enhance their ability to inhibit the enzyme GGDPS. The increased potency observed with the citronellyl ether 24 versus compounds prepared earlier, as well as the difference in activity between the two prenyl–geranyl isomers, encourage a more extensive investigation of the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• interconversions furnished diacetate 43, which could be converted to the desired natural product 44 using a three step sequence. Terpenoid targets The group of Wender applied the DVCPR in their total syntheses of (±)-confertin (50) and (±)-damsinic acid (51) [47]. A mixture a trans/cis-vinylcyclopropyllithium 46

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

•  1) are suitable substrates for allylic oxidations with PSA. Due to their interesting properties as flavor compounds, we focused our attention to the oxidation of terpenoid spiroethers. As model compounds, unsaturated spiroethers 7, 8, 11 and 12 were synthesized by the intramolecular silyl-modified

• biocatalytic oxidation of vitispirane as a terpenoid with a conjugated double bond and a sterically hindered allylic position (Figure 2). Vitispirane is a flavor compound of vanilla and quince fruit and was identified in grape juice and wine [41][42]. Various syntheses of vitispirane have been reported in the

• ). This allows the isolation of large quantities of the enantiomerically pure derivatives and their detailed olfactory analysis. Conclusion The edible fungus PSA allows efficient allylic oxidations of terpenoid olefins. The oxidation protocols are quite simple, because the lyophilisate of PSA can be used

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• zanamivir [141]. The putative biosynthesis of 156, which contains a pentacyclic ring system with a cis-fused decalin is depicted in Scheme 21. Farnesyl pyrophosphate (167), which originates from the terpenoid pathway through the condensation of dimethylallyl pyrophosphate (DMAPP, 165) with two units of

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• examples of comparing natural to artificial systems it is their interplay that may provide the best solutions to some of the most urgent problems of our time. A perfect example is artemisinin, a terpenoid natural product from Artemisia annua, which is highly efficient in the treatment of malaria. The