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

• [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial

• . In fungi and plants, they can be both class I or class II TPSs and even mixed class I/II [21]. Class I TPSs harbor two distinct catalytic motifs, which are crucial for binding and correctly positioning the substrate for catalysis, the aspartate-rich motif (DDxxD) and the NSE/DTE motif, that bind to

• enzymes that is widely distributed among plants, fungi and bacteria. CotB2 has evolved to convert the acyclic, achiral substrate GGDP to the 5–8–5 ring motif of cyclooctat-9-en-7-ol that contains six chiral stereocenters. Hence, CotB2 has been fine tuned to perform a highly specific regio- and

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• corroborated by 3JHH vicinal coupling constant (JH4,H5 = 15.8 Hz). In fungi and certain kinds of bacteria, methyl substituents in the fatty acid carbon chain or the polyketide chain are derived from the methyl group of S-adenosylmethionine (SAM) (Figure 3A) [13][14]. This methylation reaction usually occurs at

• but are widely produced by many fungi and are thought to play an important role in the interaction between fungi and their host organisms. C9-Methylated sphingolipids are also found from some marine invertebrates such as sea anemone and starfish although their biological function is still unclear in

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• isolated from fungi of the genus Acremonium. Here, we present the asymmetric total synthesis of acremine F which hinges on a modestly enantioselective dihydroxylation and a subsequent kinetic resolution via a highly selective asymmetric reduction. Chemoselective oxidation of acremine F gave access to

• acremines A and B. The dimerization of acremine F to bisacremine E was investigated but could not be achieved, shedding light on the formation of the acremine dimers in nature. Keywords: meroterpenoid; natural product; selective oxidation; total synthesis; Introduction Endophytic fungi grow in a symbiotic

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

• Benjamin Libor Henrik Harms Stefan Kehraus Ekaterina Egereva Max Crusemann Gabriele M. Konig Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany 10.3762/bjoc.15.216 Abstract Fungi are an important source of bioactive metabolites. The Fungal one-step

• IsolatioN Device (FIND) technology allows the isolation of rare fungi from terrestrial and marine samples. The FIND comprises a multi-chambered micro agar plate, where initially only one fungal part (e.g., hyphal cell, mycelial fragment or spore) is located in each chamber. After inoculation the device is

• placed back into the original natural environment of sample collection, to ensure favourable growth conditions. Experiments were carried out with terrestrial soil and marine sediment, as well as sea water samples to validate this method. This yielded axenic cultures of 12 different filamentous fungi, one

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

• the combination of genome mining and heterologous expression of predicted terpene synthases for detecting unknown terpenoids from rarely studied fungi. Results and Discussion Prediction and analysis of terpene synthase genes in T. viride J1-030 Through genome sequencing of T. viride J1-030 and

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

• fungi against plant hosts [12]. Well-known examples include the host-specific toxins victorin and T-toxin and other non-host-specific toxins such as the ophiobolins [11]. Bipolaris sorokiniana (syn. Cochliobolus sativus) has been identified as the causative agent of multiple diseases on wheat and barley

• sesquiterpenoids have been previously reported from fungi, including from Bipolaris sp. [1], B. sorokiniana [2], B. eleusines [3][4][5][6][8], Cochliobolus sp. [26], Cochliobolus sativus [18], Helminthosporium sativum [20][33][34], Drechslera sp. [27], Drechslera dematioidea [15], and Veronaea sp. [35], most of

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• ) skeletons. These azasteroids, in which one or more nitrogen atoms are present in the side chain, were designed as promising compounds since such classes of antifungal steroids were known in the literature. Some of the resulting azasteroids showed inhibitory effects on the growth of fungi such Fusarium

• pairs 18 and 19 [22]. For example, the pair of androstanic and pregnanic derivatives incorporating R1 = Phe and R2 = t-Bu showed significant activity against both fungi tested, but the compounds derived from benzylamine (i.e., R1 = Bn) did exhibit either a low or null biological activity for the fungi

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

• 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

• evolution of terpenes synthases among Streptomyces species. It would be interesting in follow-up studies to assess the distribution and evolution of these genes among other bacteria, fungi, protists and plants. In addition, a deeper knowledge of the ecological function of terpenes in bacteria and in the

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

• Site Hannover-Braunschweig, Inhoffenstraße 7, 38124 Braunschweig, Germany Junior Research Group Genetics and Genomics of Fungi, Senckenberg Gesellschaft für Naturforschung, Georg-Voigt-Str. 14–16, 60325 Frankfurt am Main, Germany Institute of Food Chemistry and Food Biotechnology, Justus Liebig

• /mL, for KB3.1 = 7 µg/mL), but was inactive against all test organisms in our standard test panel, comprising selected Gram-positive and Gram-negative bacteria as well as fungi [8]. Compound 4 was inactive in all assays of our test panel, and 3 could not be tested due to the insufficient amount

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• ], protozoa [57], and fungi [58], and totally absent in mammals. D-Arabinofuranose can only be found in prokaryotes, for example in Gram-negative bacteria where it is a cytoplasmic intermediate in the biosynthesis of 3-deoxy-D-manno-octulosonic acid (KDO), an essential carbohydrate of the cell wall

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

• that was supported by a feeding experiment with (methyl-2H3)methionine. Keywords: constitutional isomerism; gas chromatography; mass spectrometry; natural products; volatiles; Introduction Fungi release a large number of different volatiles that belong to all kinds of natural product classes [1

• also important in the interaction between different species, e.g., between ophiostomatoid fungi and conifer bark beetles that show different behavioural responses to fungal volatiles [9]. Fungal volatiles can also be of importance in the interaction between plants and fungi. In some cases, fungal

• volatiles seem to be involved in the plant pathogenicity of fungi, as recently observed for 3,4-dimethylpentan-4-olide (4), a volatile from the ash pathogen Hymenoscyphus fraxineus that currently threatens the European ash population [10]. Both enantiomers of this lactone were found to inhibit ash seed

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

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• ][7][8], and fungi [1][9][10], they can kill cancer cells [11]. So far, >2,500 AMPs have been described in the literature and only ≈10% of those are known to exhibit anticancer activity, according to the Antimicrobial Peptide Database (http://aps.unmc.edu/AP/main.php). In total, there are around 600

• -negative bacteria, fungi, and protozoa. However, both peptides presented high hemolytic activity, which limited their use as potential therapies. Torres et al. synthesized Dec-NH2 analogs with single and double substitutions, which exhibited increased resistance to degradation and lower hemolytic activity

• [9][10]. The two Dec-NH2 analogs designed to fit a leucine zipper (LZ) template [25][26] presented the lowest hemolytic activity against red blood cells and maintained the antimicrobial activity of the parent template molecule vs Gram-positive bacteria, Gram-negative bacteria, and fungi. The authors

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• of this class, bafilomycin A1 (Figure 3) is a useful biochemical tool as it prevents the re-acidification of synaptic vesicles once they have undergone exocytosis [14]. Bafilomycins are also known to be cytotoxic, inhibitors of autophagy, active against Gram-positive bacteria, yeast and fungi

• , nematodes, insects, immunosuppressant or with antitumor activities [12][13][14][15]. Therefore, lanyamycin (1/2) was tested in our screening panel against bacteria, fungi, mammalian cell cultures and for antiviral activity against HCV in human liver cells. Lanyamycin (1/2) was analyzed for antimicrobial

• activity against bacteria and fungi and showed moderate antifungal activity in addition to a good inhibition of Micrococcus luteus (Table 3). When lanyamycin (1/2) was evaluated for cytotoxicity against growing primary cell lines, mouse fibroblasts (L929), and human cancer cell lines, nasopharyngeal cells

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• , 1 yeast, and 4 fungi. The result of this screening prompted the detailed chemical study of a strain coded as MBAF1239, which resulted in the isolation of eight antibacterial metabolites, including the two new 2-alkylquinolones 1 and 3 (Figure 1). Strain MBAF1239 was seed-cultured in V22 medium and

• and 8. Among 1–6, the 2-heptenyl-3-methyl congener 4 was the most active. Compounds 3–6 also inhibited the growth of the fungi R. oryzae and T. rubrum, while 1 and 2 did not. This may to some extent attributable to the global lipophilicity of molecules, as 1and 2 are among the fastest eluting

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

• 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

• aflatoxin from Aspergillus flavus [3] or the amatoxins from the death cap (Amanita phalloides) [4] are extremely toxic for humans. Recently, also volatile secondary metabolites from fungi attracted considerable interest [5][6]. Volatiles not only contribute to the pleasant aroma of edible mushrooms such as

• the penny bun (Boletus edulis) [7], but can also inhibit the growth of other fungi [8] which likely contributes to the induction of systemic resistance in plants by Trichoderma [9]. Fungal volatiles can also act as self-inhibitors of fungal germination [10] or as attractants for insects involved in

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• research during the past decades has shown that many fungi release a rich bouquet of volatile organic compounds [1]. Some of these metabolites contribute to the pleasant aroma of edible mushrooms, e.g., the widespread compound oct-1-en-3-ol (1) is responsible for the typical odour of the button mushroom

• (2), another widespread fungal volatile, a plant growth promoting effect and an induction of systemic resistance in plants against fungi was observed [5]. The significant biological effects of these and other fungal volatiles recently resulted in a considerable interest of natural product chemists

• to select a culture initiated from the germinating ascospores of H. invadens among a panel of hypoxylaceous fungi that were studied for comparison of their volatile profiles [13]. Several aromatic compounds were detected in the headspace extracts of Hypoxylon invadens MUCL 54175 for which an

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ]. These o-QM precursors by a thermal elimination of dimethylamine were then reacted with different cyclic dienophiles to give various inverse electron-demand Diels–Alder adducts 35–37. In case of 36, the cis-fused ring system found to be similar to bioactive xyloketals isolated from fungi (Scheme 4) o-QMs

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• ] reported that a fungal strain (Fusarium equiseti M41) was able to introduce a 7β-hydroxy group into LCA by hydroxylation forming UDCA directly. Later, many other microorganisms with a 7β-hydroxylating activity were discovered in strains of actinobacteria and filamentous fungi [96][97]. The key-enzyme in

• that pathway is a P450-like enzyme that catalyses the specific and irreversible 7β-hydroxylation. On this topic, a recent work by Kollerov et al. [98] describes several DCA modifying filamentous fungi strains (mostly ascomycetes and zygomycetes): the highest 7β-hydroxylase activity level was found in

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

• compound that was first isolated from Tricholoma matsutake and named “matsutake alcohol” [2][3]. This odourous volatile is responsible for the typical mushroom smell of many fungi and also contributes to the pleasant aroma of edible mushrooms such as the button mushroom, Agaricus bisporus [4]. Another

• widespread fungal volatile is 6-pentyl-2H-pyran-2-one (2) that was first isolated from Trichoderma and exhibits a strong coconut aroma [5]. For fungi producing 2 a plant-growth promoting effect and an induction of systemic resistance in plants has been observed which makes these fungi interesting as

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• . The receptors of the innate immune system can detect particular components present in bacteria, viruses or fungi which are designated as “pathogen associated molecular patterns” (PAMPs) [1]. These receptors, termed pattern recognition receptors (PRRs), are able of sensing and responding to PAMPs. The

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

• were mainly reported from plants and, to a lesser degree, also from fungi and marine invertebrates. In recent years, however, the discovery of terpenoids from prokaryotes has gained momentum. The ease of DNA sequencing has strongly favored this development, contributing to the identification of

• an agar diffusion assay against a standard selection of Gram-positive and Gram-negative bacteria as well as some fungi. However, the compound was inactive at all tested concentrations. A literature search revealed that 1 is the first microbial terpene possessing an octahydro-1H-indene backbone

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• the obtained compounds are active against Gram-positive bacteria and Candida type fungi. Keywords: antimicrobial activities; D-galactosamine; diosgenin; glycosylation; saponin; tetrachlorophthalimido derivatives; Introduction Saponins are steroid or triterpenoid glycosides found in various plants [1

• diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside 7 is active solely against E. faecalis. In contrast to 7, the N-acetyl saponin 6 was found to inhibit the growth of all the tested fungi and bacteria with MICs of 8–32 μg/mL. Among the three ureido derivatives of 4, solely diosgenyl 2-(2-chloroethylureido)-2

• 9 exhibits weak inhibitory activity against tested Gram-positive bacteria. Its ethylureido analog 8 is inactive in respect of both fungi and bacteria, likewise phenylureido derivative 10. It would seem that an electronegative Cl atom improves the inhibitory properties of ureido saponins against Gram

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• [39] or Mangifera indica [40] (Figure 4). Fungi C-glycosyltransferases were also identified in Streptomyces, including UrdGT [41][42] and SsfS6 [43] that catalyse the transfer of the unusual D-olivosyl carbohydrate moiety on the aglycon acceptor. Bacterial C-GTs are the last group identified in

• found in maize (UGT708A6), rice (OsCGT), buckwheat (FeCGT), Mangifera indica (MiCGT), Arabidopsis thaliana (AtCGT), fungi (UrdGT2 and SsfS6) or bacteria (iroB). General mechanisms of the O-GHs-catalysed hydrolysis. Neighbouring group participation mechanism of retaining the O-GHs-catalysed hydrolysis

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• . Conclusion Benzopyranones are widespread in nature, being found in a wide variety of organisms, including fungi, and are endowed with a broad-spectrum of biological activities [8]. Also benzofuranones are found in nature, for example the paecilomycins/aigialomycin group of natural products co-exists with