Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• metabolite; Xenorhabdus; Introduction The constantly increasing threat of multiresistant pathogens requires the development of new antibiotics, as they are indispensable to maintain the state of health of our society [1]. Bacterial natural products, also called secondary or specialized metabolites (SM

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• particular group of compounds of particular focus in our research activities are natural products with enamide moieties [11]. Among these, chondrochloren having a (Z)-enamide moiety features a rare structural motif. The myxobacterial metabolite chondrochloren A (1) was isolated from Chondromyces crocatus

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• metabolite profiles using analytical HPLC coupled with diode array detection and mass spectrometry (HPLC–DAD–MS) revealed that the production of pigmentosin B (2) was apparently specific for Gibellula sp., while the glycoasperfuran 3 was specific for C. javanica. Keywords: antibiofilm agents; natural

• bioactive secondary metabolites. Herein, we report on the isolation, structure elucidation, and biological activities of six compounds from Gibellula sp. and Cordyceps javanica. Furthermore, the species-specific patterns of secondary metabolite production were studied. Results and Discussion Structure

• the secondary metabolite production among species of Cordycipitaceae, HPLC–UV–vis profiles of all fungal isolates were generated and compared to each other. This revealed that the individual species possessed unique secondary metabolite profiles. Pigmentosins A (1) and B (2) were detected in all

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• polyketide; Fusarium; marine fungus; secondary metabolite; sponge; Introduction Marine organisms have been known as a potential source of prospective bioactive compounds, and sponges are particularly emphasized as the most promising source among all marine invertebrates [1][2]. However, the collection of

• metabolite of the fungus Geosmithia [24]. Plant metabolites, feralolide and its glycoside, possessing the same skeleton as 2 were reported from the medicinal herb Aloe vera [29], but this carbon skeleton is novel as a fungal secondary metabolite. Experimental General experimental procedures NMR spectra were

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

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

• synthetic biology to engineer pathways that will expand molecular diversity, especially around scaffolds associated with high-value compounds. The biosynthetic logic of terpene formation differs significantly from the logic employed by other classes of secondary metabolite biosynthetic pathways. Bacterial

• lividans, under the control of exogenous promoters [92][93][94]. To minimize the cellular resource competition and facilitate cleaner analysis, many of these hosts have been engineered to remove native secondary-metabolite BGCs and for optimized terpene precursor supply [1][95][96][97]. Like Streptomyces

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

• by Skeletocutis. Interestingly, tyromycin A (6) was found to be the only common metabolite in fruiting bodies and mycelial cultures of the fungus, and none of the recently reported skeletocutins from the culture of the same strain were detected in the basidiomes. Keywords: basidiomycete

• MUCL56074. We have recently reported the known metabolite tyromycin A (6), together with 12 unprecedented congeners for which we proposed the trivial names skeletocutins A–L, which were obtained from a liquid culture of the same fungus [4]. A preliminary characterization of the producer organism suggested

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

• 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

• library (>7,100 standards) also failed to provide a single known secondary metabolite, further suggesting the strain was a hitherto unaccounted species of Aspergillus. A. nanangensis was cultivated separately on jasmine rice and pearl barley for 21 days, which resulted in confluent and thick mycelial

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

• . Prof. Soedarto SH., Semarang 50275, Central Java, Indonesia 10.3762/bjoc.15.225 Abstract (2Z,4E)-3-Methyl-2,4-decadienoic acid (1) was identified as a major metabolite from a culture extract of a marine bacterium Microbulbifer which was collected from a stony coral Porites sp. NMR-based spectroscopic

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

• -dimethyl-4-oxobicyclo[3.1.1]hept-2-en-6-yl)pent-2-enoic acid, for which the trivial name heydenoic acid A is suggested. Notable is the occurrence of peaks containing m/z values attributable to isomers of the isolated metabolite. Compound 2 has a molecular formula of C15H22O3, (HRESIMS m/z: 251.1641 [M + H

• environment. Halotolerance was to date exclusively reported for members of the Cladosporium sphaerospermum complex [28]. Analysis of genes involved in secondary metabolite production suggested Cadophora malorum as a producer of bioactive compounds [29], as later confirmed by the results of Almeida et al. [30

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• anti-inflammatory activity of compound 1 using rat macrophages. Results and Discussion L. archangelica metabolite isolation and identification For isolation of the major metabolites of L. archangelica, we used 100 g of fine ground seeds (Supporting Information File 1, Figure S2) and the method of

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

• can serve as the starting material to a variety of orthogonally protected derivatives of 2,3-diaminopropanoic acid. The bicyclic amino acid (S)-127 is a major metabolite of isazofos in corn grain and for toxicological studies both enantiomers were required [17]. To this end the aziridine ester (2S,1′R

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• . Sulfone 8 was a relatively minor metabolite, at only 10% of sulfoxide 6. A chiral HPLC (IC column, solvent: 5% isopropanol in hexane; 1 mL/min) enantiomeric assay was conducted for sulfoxide 6 and the outcome compared with a racemic sample of 6, prepared by chemical oxidation of thioether 4 [22]. Although

• metabolised. Product profiles were again determined by HPLC analysis and relationships are summarised in Scheme 2. Incubation of racemic sulfoxide 6 led to a similar outcome to that for 4 with the formation of phenol sulfoxide 7 and phenol sulfone 8 suggesting that sulfoxide 6 is the first formed metabolite

• sulfoxide 6 to sulfone 9 in these re-incubation experiments. It may be that there is a barrier to uptake of the phenols into the fungal cells and that they are actively exuded when generated within the cell. As a final experiment sulfone 9, which was not observed as a metabolite, was prepared by mCPBA

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

• domain organization of the two corresponding biosynthetic assembly lines further indicated that Massilia sp. NR 4-1 does not produce micacocidin, but a derivative of this secondary metabolite. The isolation of siderophores from microorganisms is usually straightforward due to their iron-dependent

• increased in the extract from the iron-deficient culture (Figure 1C). The corresponding metabolite, which is in the following referred to as massiliachelin (1), was subsequently isolated by HPLC. High-resolution ESIMS of 1 yielded a pseudomolecular ion peak at m/z 467.2033 [M + H]+, which indicates a

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

• , as they were present in all except one of the Streptomyces species (S. pactum KLBMP 5084) (Figure 1). This finding suggests that geosmin may have an important ecological function as a chemical signal or as protective specialised metabolite against biotic and abiotic stresses, similarly as the roles

• [33]. Therefore, these results could also be interpreted as evidence for a rapid evolution of secondary metabolite genes to create new natural products with beneficial ecological functions for the producing organism. While many streptomycetes produce geosmin as a major metabolite of their bouquets of

• transfers of terpene synthase genes in Streptomyces, but could also point to secondary metabolite genes as being less conserved than housekeeping (primary metabolism) genes. Rapid evolution of secondary metabolism can lead to new natural products with advanced ecological functions in specific ecological

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

• secondary metabolite profiles of C. aegerita, we found several terpenoids in submerged cultures. Aside from the main metabolite, bovistol (1), two new bovistol derivatives B and C (2, 3) and pasteurestin C as a new protoilludane (4) were isolated by preparative HPLC. Their structures were elucidated by mass

• Discussion Both the ethyl acetate extract of the culture filtrate and the acetone extract of the mycelium of C. aegerita, grown in ZM/2 medium, contained a major metabolite with a molecular mass of 496 Da, as detected by HPLC–MS analysis. Its molecular formula C30H40O6 was deduced from its [M + Na]+ peak at

• bovistol, which was confirmed by the elucidation of the structure by COSY and HMBC NMR data [5]. In the course of the isolation of 1 the minor metabolites 2 and 3 accrued. Metabolite 2 was analysed for a molecular weight of 478 Da. Its molecular formula C30H38O5, deduced from HRESIMS data, indicated the

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• cycle. To overcome the problem of unwanted malyl-CoA accumulation, a malyl-CoA thioesterase [59] had to be added to the synthetic network. This enzyme effectively recycles the dead-end metabolite back into two intermediates of the network, malate and free CoA, thus serving as a “proof-reading” enzyme at

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• (Scheme 41). In 2015, Tyagi’s group presented a biomimetic synthesis of metabolite 149 from intermediate 148 by using catalytic vanadyl acetylacetonate and molecular O2 (Scheme 42) [122]. The transformation went through aerobic oxidation ring-opening of cyclopropanols. The results showed that the oxygen

• for the synthesis of metabolite. Acknowledgements The work was supported by the National Nature Science Foundation of China (Grant No. 21602056), Scientific Research Fund of Hunan Provincial Science and Technology Department (Grant No. 2018JJ3208), Scientific Research Fund of Hunan Provincial

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• (HHQ, 1) are important signaling molecules involved in quorum sensing and as such play an important role in virulence regulation [3][10][11][12]. Another metabolite from the AQ biosynthesis pathway of P. aeruginosa is 2-heptyl-1-hydroxy-4(1H)-quinolone (generally referred to as 2-heptyl-4

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• is detected as metabolite in vivo in biochemistry [15], and is known to react in the atmosphere to afford the secondary organic aerosol as air pollutants [16]. Among the four diastereomers of LMdiols (Figure 2), 2b and 2c have already been reported [14][17][18][19][20]. Conversely, the distinct

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

• components of complex extracellular metabolite mixtures. The reported compounds are specific for Roseobacter group bacteria of the genera Roseovarius and Loktanella, in contrast to broadly distributed AHLs. Although their function as signalling compounds is not proven, the occurrence of 2-aminobutyric acid

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• assumedly may not need to target the active site of the enzyme, but rather a different pocket or surface. To this end, further research on the exact molecular mechanism of the regulatory activity of PqsE is needed. PqsBC The small molecule 2-AA (27), which is also a secondary metabolite generated in the AQ

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , as they possess biologically validated structures, which could become suitable leads in drug discovery [2]. Recently, our research group reported the first total synthesis of leopolic acid A (Figure 1), a fungal metabolite from a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of

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

• conclusions drawn attributing bioactivities such as antifeedant activity to this chemical reactivity [1][11][12][13]. In an effort to ascertain whether the mollusc metabolite onchidal is susceptible to nucleophilic attack in a similar manner, herein we report on the reactivity of onchidal and a library of

• low reactivity as determined from the n-pentylamine incubation studies. Conclusion A chemical reactivity study of the opisthobranch mollusc metabolite onchidal (6) has identified that it can react with amines to form pyrrole products. The reaction was presumed to proceed via amine-mediated conversion

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• approach was concomitantly undertaken by groups from Japan and Austria, respectively [41][42], aiming at the synthesis of the bacterial metabolite and potent innate immune modulator D-glycero-β-D-manno-heptose-1,7-bisphosphate (43, HBP, Scheme 7). The group around Zamyatina employed 2,3,4,6-tetra-O-acetyl