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

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

• Bochum, Germany 10.3762/bjoc.14.132 Abstract Lanyamycin (1/2), a secondary metabolite occurring as two epimers, was isolated from the myxobacterium Sorangium cellulosum, strain Soce 481. The structures of both epimers were elucidated from HRESIMS and 1D and 2D NMR data and the relative configuration of

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

• in fungi [34]. Conclusion The genus Hypoxylon has already been examined extensively for secondary metabolite production, and some of its species like H. pulicicidum and H. rickii are extremely creative with respect to the production of non-volatile compounds [35][36][37]. The current study is the

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

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

• subject to enzymatic modifications in their native producers. The exclusive testing of a terpene cyclase might hence unveil a biosynthetic intermediate rather than the final product of a secondary metabolite pathway [5][6]. To avoid this problem, we here describe a method for the identification of

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

• alcohol that can easily be isolated by extraction and column chromatography, which underpins the potential of plants, besides the recently reviewed microbial hosts for the sustainable production of diterpenes [36], as expression systems for secondary metabolite genes. The function of the investigated

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

• –46.7, c 0.9 in chloroform) for the cembranoid bisepoxide isolated from the soft coral Sarcophyton sp., pointing towards the same structure for this secondary metabolite. However, no 2D NMR data or stereochemistry of this molecule was reported up to now. Here we include the results of 2D NMR (COSY, HMBC

• supporting this hypothesis. Besides our earlier study [12] reporting a feeding deterrent activity of 4-oxochatancin (16), only a study by Slattery et al. [15] could show an antifeedant effect of a secondary metabolite sequestered by Phyllodesmium. In the latter study, acetoxypukalide, which was sequestered

• . Taking the metabolites detected by UPLC–HRMS analysis also into account, P. longicirrum demonstrates an unprecedented level of secondary metabolite diversity. The herein studied P. longicirrum sequesters its secondary metabolites most probably from the chemistry-rich S. glaucum species complex, in

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• regio- and enantioselectivity. Disclosed herein, this discovery has enabled the first total synthesis of (−)-anverene (1) (Scheme 1, bottom), a secondary metabolite from the algae Plocamium cartilagineum with selective antibiotic activity against vancomycin-resistant Enterococcus faecium (VREF) [10

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• for a number of characterised secondary metabolite pathways. For example, the bottromycin gene cluster encodes two stand-alone YcaO domain proteins that have been postulated to participate in heterocyclisation reactions [10][11][12][13]. Lanthionine bond formation in lanthipeptides Lanthipeptides

• that have been characterised for both RiPPs and for other secondary metabolite pathways, but it is interesting to note that there are a significant number of biochemical modifications that, thus far, appear to be unique to RiPP biosynthesis. For example, lanthionine formation, YcaO protein-catalysed

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

• that large genomes often correlate with the potential for prolific secondary metabolite production by revealing almost 8.6% of the genome to be possibly involved in the biosynthesis of secondary metabolites [36]. Mining this genome for the presence of PKS and NRPS genes exposed 18 biosynthetic clusters

• of compounds that have recently been shown to have antiproliferative effects on leukemic K-562 cells [27]. Halotolerant and halophilic marine myxobacteria are poorly investigated regarding secondary metabolite production. Therefore, the pool of secondary metabolites isolated from organisms of this

• osmolytes like betaine and ectoine were detected in the halotolerant bacterium. Taxonomy, cultivation and secondary metabolite chemistry of marine-derived myxobacteria (Nannocystineae) The following sections summarize features of three halotolerant and three marine-derived bacterial taxa clustered in the

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• aglycone to be a sesquiterpene [33]. Based on previous reports, the signals of a CH group at δ 2.12/65.2 (C-10) and a quaternary carbon at δ 53.8 (C-6) observed in the NMR spectra of compound 1 suggested a trixane scaffold for this secondary metabolite [34]. C-10 and C-6 are respectively shared by two and

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• presence of putative secondary metabolite gene clusters using the publicly available online tool antiSMASH 3.0 [51]. This analysis revealed that all strains possess extraordinary capacities for natural product assembly. Interestingly, however, the number of biosynthetic loci is not linearly correlated with

• the genome size. The largest number of secondary metabolite gene clusters was found in Corallococcus coralloides DSM 2259 and not in the two Sorangium cellulosum strains, although the latter feature significantly larger genomes (Table 1). When the number of detected loci is related to the genome size

• of biosynthesis gene clusters provide no information about the identity or biological role of the associated natural products, we note that predatory myxobacteria possess a higher density of secondary metabolite gene clusters in their genomes than their non-predatory relatives. But are these clusters

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• of myxovalargin (1), a secondary metabolite from Myxococcus fulvus with antibacterial activity [14][15], we report on copper-mediated cross-coupling chemistry to create peptide fragments bearing dehydrovaline and dehydroisoleucine. We faced difficulties to use the reported conditions for the C–N

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• molecular analysis of the biosynthetic gene cluster of pederin (3) [49][50][51][52]. Beetle larvae hatching from pederin-containing eggs were less prone to predation by wolf spiders than pederin-free larvae, indicating the ecological significance of this secondary metabolite [53]. The biosynthetic gene

• typical for all other attine ant fungi. The fungus was found to produce several antifungal diketopiperazines (e.g., 33) [114]. In another study, also reported by Clardy and co-workers, the secondary metabolite profile of the symbiotic fungus Bionectria sp. associated with the fungus-growing ant

• summary, entomopathogenic fungi are rich in secondary metabolite gene clusters, some of which have been genetically characterized. However, the vast majority of the encoded compounds, as well as their biological role(s) remain uncovered [137]. In light of the rapidly declining costs for -omic technologies

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• ]. Synthesis of ascididemin (42) The first synthesis of ascididemin was performed in 1992 by Moody et al. [64] and included four steps with an overall yield of 21%. Recently, the same secondary metabolite was prepared by six efficient steps which afforded a yield two-fold (45%) of that of the previous

• using phosphoryl bromide. Another organozinc substrate was coupled to the obtained intermediate by a Negishi cross-coupling and cyclisation occurred to give the expected secondary metabolite (Scheme 8) [68]. The yield of the last step in the preparation of 9 could be improved by using the synthetic

• tryptophan (61a) and dopamine (66) performed by Steffan et al. established these two chemical entities as precursors of shermilamine B (67), a secondary metabolite produced by tunicates. Consequently, the authors postulated that tryptophan was transformed into kynurenine (62), which was in turn

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• provided close to 20 hormaomycin analogues that have contributed to an understanding of the biosynthetic pathways, the conformational behavior in solution and the structure–activity relationship. After the initial observation that hormaomycin (1) has a marked influence on the secondary metabolite

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• alga was achieved in a fast, simple, and inexpensive manner, which offers a useful option when consumers wish to enjoy the crispy texture of fresh alga, but feel uneasy about the possibility of food intoxication. Conclusion We explored a bioactive secondary metabolite from the very rare but edible

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• species in a secondary metabolite study [2]. Recently, El-Neketi et al. [5] described the isolation of two new tanzawaic acids G and H, as well as tanzawaic acids B and F and arohynapene D from an endophytic Penicillium citrinum species. Therefore, Penicillium sp. IBWF104-06 appears to be related by its

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• µM (1.3 µg/mL). Moreover, it also reduced mRNA levels and protein synthesis of survivin and triggered apoptosis. Keywords: apoptosis; inhibitor; natural products; secondary metabolite; structure elucidation; survivin; Introduction Survivin, a member of the inhibitor of apoptosis (IAP) protein

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• Stigmatella aurantiaca MYX-030 resembles the secondary metabolite profile of previously chemically investigted S. aurantiaca and S. erecta strains. Interestingly, both, S. aurantiaca Sg a15 and S. erecta Pd e21, were reported to produce 5-nitroresorcinol (13) [36]. The biosynthesis of 13 was investigated in S

• order to identify further myxocoumarin producing strains, chemical screenings of the secondary metabolite profiles of S. aurantiaca Sg a15 and S. erecta Pd e21 using the fermentation conditions identified for S. aurantiaca MYX-030 might thus be worthwhile. To verify the initially measured antifungal

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• which the absolute configuration was only assigned based on analogy to related natural products are stagonolide E [28][29] and curvulide A [30]. Stagonolide E is a secondary metabolite of Stagonospora cirsii, which is a fungal pathogen of the weed Cirsium arvense [28]. It has also been isolated from the

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

• allows for a rapid access to a variety of members of the cytochalasin alkaloid family. The power of the intramolecular Diels–Alder strategy for the synthesis of the isoindolinone moiety was also recognized during the synthesis of aspergillin PZ (91) [73]. This secondary metabolite has a remarkable

• basis of the structural similarity between 208 and marinopyrrole A, another secondary metabolite derived from a marine Streptomyces species [156]. The common biosynthetic precursor 206 stems from a mixed nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) pathway. The amino acid proline is

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

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

• fascinating as is spectacularly demonstrated by the prominent examples of maitotoxin [3], the largest non-polymer secondary metabolite known to date, or calicheamycin (Figure 1), which possibly holds the record in carrying the most diverse functional groups including an enediyne subunit, a deoxysugar, an

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• previously identified and characterized compounds has become a serious impediment to the discovery of new bioactive natural products. Here, genetic knockout of an unusual non-ribosomal peptide synthetase (NRPS) C-PCP-C module, aziA2, is performed resulting in the accumulation of the secondary metabolite

• implemented to “activate” secondary metabolite production [4][5]. In some instances, shot-gun cloning and expression of soil samples and bacterial symbiont genomes have led to the discovery of a representative set of natural products and enzymes, albeit typically of small biosynthetic pathways (less than 10

• or cryptic metabolites for subsequent isolation and characterization. Secondary metabolite production by microorganisms is often viewed as a line of defense against competing microbes for nutrients. Natural products like azinomycin, a DNA crosslinking agent, can offer a means of protection to the

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• , exhibited an extremely different secondary metabolite composition. In particular, this second specimen has been found to be rich in polypeptides and, from the CHCl3 phase of the organic extract, we have identified the major member of this class as theonellapeptolide Id (1) (Figure 1). In this paper we