Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• Saarbrücken, Germany 10.3762/bjoc.15.286 Abstract The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• isolated and characterized five previously undescribed secondary metabolites, skeletocutins M–Q (1–5), along with the known metabolite tyromycin A (6) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic, or nematicidal activities. However

• , compound 3 moderately inhibited the biofilm formation of Staphylococcus aureus (S. aureus), while compounds 3 and 4 performed moderately in the ʟ-leucine-7-amido-4-methylcoumarin (ʟ-Leu-AMC) inhibition assay. These compounds represent the first secondary metabolites reported to occur in the fruiting bodies

• ; polyporaceae; secondary metabolites; structure elucidation; Introduction Over the past years, we have been studying the secondary metabolites of African Basidiomycota that were collected in rainforests and mountainous areas of Western Kenya. These species were new to science, and proved to be a prolific

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

• production of terpenoids as the dominant biosynthetic class of secondary metabolites. Results and Discussion Purification and identification The metabolite profile of A. nanangensis was examined on a limited range of solid and liquid media suitable for fungal metabolite production. The metabolite profile

• Aspergillus type species) and unidentified but metabolically talented fungi (>60,000 spectra from 3,000 species) returned no similar metabolite cohorts, suggesting an unknown species. Individual retention time/UV–vis searches of the dominant 15 secondary metabolites against our in-house pure metabolite

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

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

• secondary metabolites have received lesser attention [3]. To date, a couple of new compounds were discovered from soft coral-associated bacteria such as pseudoalteromones from Pseudoalteromonas isolated from the cultured octocoral Lobophytum crassum [4][5] and macrolactin V from Bacillus amyloliquefaciens

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

• relationship with their plant hosts [1], which is mediated by secondary metabolites [2]. In 2005, Torta and co-workers reported the isolation of six meroterpenoid natural products, acremines A–F from A20, a strain of Acreonium byssoides, isolated from grapevine leaves that were artificially inoculated with

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

• adaption of the respective strains to marine conditions (see Supporting Information File 1, Tables S1 and S2 for full experimental data). With the FIND technology we managed to isolate rare fungi. To evaluate the potential for the biosynthesis of bioactive secondary metabolites we performed screenings on

• chemically diverse secondary metabolites in the major VLC fraction 3. Detailed HRESIMS investigation was thus performed with VLC fraction 3, which showed prominent m/z values for metabolites with molecular weights of 248 and 250 Da. Subsequent repeated fractionation of VLC fraction 3 by RP-HPLC resulted in

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

• that has received considerable attention as an effective biocontrol agent against two fungal pathogens, Fusarium oxysporum f. sp. adzuki and Pythium arrhenomanes, infecting soybean. This fungus is a competent mycoparasite and strong producer of secondary metabolites [22][23]. However, T. viride

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

• array of secondary metabolites, including sesquiterpenes [1][2][3][4][5][6][7], sesquiterpene-xanthones [8], diterpenes [9], sesterterpenes [10], cochlioquinones and peptides [11]. Moreover, several of these secondary metabolites are known to play important roles in mediating the virulence of these

• horizontal gene transfer [14]. To date, only three studies have explored phytotoxins from B. sorokiniana [2][7][10]. Therefore, in the framework of furthering our understanding of the roles of B. sorokiniana secondary metabolites in crop disease, we investigated the compounds produced by the ToxA-containing

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• the chemistry of the genus Massilia, in general. Because natural product-competent microorganisms typically synthesize multiple compounds [7], strain NR 4-1 appeared as a promising candidate to find further secondary metabolites. Further incentive for the chemical analysis of this bacterium came from

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

• remarkable genetic potential to produce a large variety of secondary metabolites with different functions including antibiotics, antifungals, pigments or immunosuppressants [1][2][3]. These are compounds of diverse chemical nature such as polyketides, peptides, aminoglycosides or terpenoids [4][5

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

• ) is one of the most praised cultivated edible mushrooms and is being cultivated at large scale for food production. Furthermore, the fungus serves as a model organism to study fruiting body formation and the production of secondary metabolites during the life cycle of Basidiomycota. By studying the

• 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

• liquid culture and could eventually serve as hosts for heterologous production of secondary metabolites derived from other Basidiomycota that are more difficult or even impossible to culture. With these goals in mind, we have initiated extensive studies of the secondary metabolism of the aforementioned

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

• sesquiterpenoids and diterpenoids with various intriguing carbon skeletons, such as nardosinanes, neolemnanes, and ylanganes [10]. Many of these secondary metabolites have attracted a lot of attention for further synthetic and pharmacological studies due to their potent bioactivities ranging from neuroprotective

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• multiple phenolic functionality. These natural products that form as secondary metabolites on a branch of flavonoid biosynthesis found wide interest for their various biological effects like anti-oxidative and biofouling-preventing activity [1]. From crude extracts of the Mongolian medicinal plant

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• to antineurodegenerative activities [2][3]. The majority of natural coumarins are secondary metabolites isolated from plants [5][6][7]. A commonly used taxonomy for these natural products (which has been extended to the non-natural analogues) is based on the coumarin structure (Figure 1) [4][8]. It

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

• mycotoxins [2], a class of highly bioactive secondary metabolites that belong to the strongest known inhibitors of protein biosynthesis in eukaryotes [3]. Similarly, the sesquiterpene aristolochene (2) is the parent hydrocarbon of PR toxin [4][5] and has been used as a marker to differentiate between toxin

• in secondary metabolites [20], but not much is known about volatiles from these fungi [21]. In continuation of this work, here we present the volatiles emitted by Hypoxylon griseobrunneum MUCL 53754 and Hypoxylon macrocarpum STMA 130423. These strains were selected, because both species released a

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• habitats with a broad metabolic potential [4][5][6][7]. Especially attached-living roseobacters produce diverse secondary metabolites, e.g., N-acylhomoserine lactones (AHLs) that the bacteria use for communication by quorum sensing [8][9][10]. AHLs are extensively investigated because of the broad

• , interpretation of mass spectra, and verification by synthesis. Results and Discussion The secondary metabolites released by liquid cultures of various roseobacters were collected by extraction via Amberlite XAD-16 resin and analysed by GC/MS. Four of these strains, Roseovarius sp. D12_1.68 and Loktanella sp. F13

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• of spinosyns via chemical modification [18]. Bioactivities of many microbial secondary metabolites are highly dependent on their sugar constituents which are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases [19]. Therefore, bioactivities of these metabolites could

• . Particularly, the compound 8b was approximately as active as spinosad. Carbohydrate substituents are considered to be related closely to many secondary metabolites [19], hence, C17–O glycosyl analogues are regarded as efficient insecticides that are likely to rival present insecticides. However, as noted in

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• organic compounds are, like all natural products/secondary metabolites, staggeringly diverse with respect to their natural source and their level of structural complexity. As part of their molecular architecture, sulfur can appear in the form of various functional groups and oxidation states: thiol

• fascinating biosynthesis of sulfur-containing secondary metabolites can be found in a recent review by Hertweck and co-workers [9]. 2. β-Hydroxy sulfides β-Hydroxy sulfides, often in disguised form, comprise a significant segment of sulfur-containing natural products, with a few examples shown in Figure 2

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 which were found to exert anti-HIV activity while sorazolones, argyrins and tubulysins showed antitumor activity or cytotoxicity [4][5][6][7][8]. In our studies on the secondary metabolites of Sorangium cellulosum (strain Soce 481), we observed strong antifungal activity in the raw extract. On RP

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

• association with animals or plants as pathogens or symbionts and exhibit a variety of catabolic and metabolic activities [1][7]. One hundred ten secondary metabolites have been reported from Burkholderia (data retrieved from the Dictionary of Natural Products, as of March 20, 2018). However, it is likely that

• Burkholderia produce many more secondary metabolites than reported, as this group was previously classified into the genus Pseudomonas [8]. In fact, the high capacity of Burkholderia in secondary metabolism is demonstrated by the presence of unique functionalities, such as monocyclic 3-pyrazolone [9], α

• culture was inoculated into 100 mL of the IMM-HS production medium (glucose 1%, K2HPO4 0.36%, KH2PO4 0.41%, MgSO4·7H2O 0.02%, CaCl2·2H2O 0.01%, FeSO4·7H2O 0.002%, NH4Cl 0.1%, biotin 0.0001%, and L-histidine 0.4%), and shaken at 200 rpm at 30 °C for 4 days. For the extraction of secondary metabolites, 100

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• on surfaces [3]. They can produce a variety of secondary metabolites, including antibiotics [4][5], volatile compounds [6][7], oligohydroxybutyrates [8] and a range of N-acylhomoserine lactones (AHLs) [8][9][10]. AHLs are quorum-sensing signaling compounds that are used for cell–cell communication to

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

• productive and biosynthetically exceptionally creative source of secondary metabolites from all classes of natural products. Many prominent compounds such as lovastatin from Aspergillus terreus [1] or the penicillin antibiotics from Penicillium [2] are used for human wellfare, whilst others including

• 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

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

• and ecologists in volatile secondary metabolites. Volatile natural products can efficiently be captured on charcoal filter traps by using a closed-loop stripping apparatus (CLSA) [6] or on polydimethylsiloxane fibres by application of the solid phase micro-extraction method (SPME) [7], followed by GC

• Xylariaceae, but has recently been reassigned to the Hypoxylaceae. This family was resurrected as a result of intensive polyphasic studies on the biological and chemical diversity of the ascomycete order Xylariales, which is well-known for its diversity of bioactive secondary metabolites [11][12]. We decided

• first to embark on the volatiles from a fungus that was assigned with certainty to this genus. A few other recent papers were dealing with volatile secondary metabolites from endophytic isolates, but these were only tentatively assigned to the genus Hypoxylon, on the basis of generation of internal

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

• Fusarium fujikuroi and other fusaria [11][12]. The potential beneficial bioactivity and role in the intra- or interspecies communication as well as the possible function as markers for toxin production recently resulted in an increasing interest in volatile secondary metabolites in the scientific community

• volatile secondary metabolites from Xylariales. Most respective studies have been dedicated to some endophytic strains that can be assigned to the Xylariales based on preliminary molecular phylogenetic data and are being referred to the suggested genus Muscodor. However, this genus was recently rejected