Gundela Peschel

Divergolides A–D from a Mangrove Endophyte Reveal an Unparalleled Plasticity in ansa‐Macrolide Biosynthesis

Herein we report the isolation, structure elucidation, andbiologicalactivitiesoffournovelansamacrolides,whichpointtoahighly divergentbiosynthetic pathwayin an endophyte ofthe mangrove tree Bruguiera gymnorrhiza. B. gymnorrhiza isone of the dominant mangrove species along the Chinesecoast, and in Chinese traditional medicine the bark and theroot of the tree is used to treat diarrhea, throat inflammation,and hemostasia.

Kandenols A-E, eudesmenes from an endophytic Streptomyces sp. of the mangrove tree Kandelia candel.

Five novel eudesmene-type sesquiterpenes, kandenols A-E (1-5), have been isolated from Streptomyces sp. HKI0595 derived from the mangrove plant Kandelia candel. Their structures were established through NMR and mass spectrometry, and absolute configurations were established by the Mosher method and comparison of CD spectra with α-rotunol and β-rotunol. The kandenols are reminiscent of various plant-derived eudesmenes, yet kandenols B and C are unusual because of their hydroperoxide moieties. Kandenol E is the first bacterial agarofuran, which belongs to an important group of antibiotics. Whereas the kandenols display no cytotoxicity against 12 human cell lines, weak to moderate antimicrobial activities were detected against Bacillus subtilis ATCC 6633 and Mycobacterium vaccae IMET 10670.

Pyrrole and indole alkaloids from an endophytic Fusarium incarnatum (HKI00504) isolated from the mangrove plant Aegiceras corniculatum

Two new pyrrole alkaloids, N-[4-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-butyl]-acetamide (1) and N-[5-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-pentyl]-acetamide (2), and a new indole derivative (3aR,8aR)-3a-acetoxyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol (3) were isolated, together with ( − )-3a-hydroxyfuroindoline, (3aR,8aS)-1-acetyl-1,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-3a-ol, and N-acetyltryptamine A, from an endophytic ascomycetous fungus, Fusarium incarnatum (HKI00504), which was isolated from the mangrove plant Aegiceras corniculatum. The structures of compounds 1–3 were determined on the basis of extensive spectroscopic data analyses.

Biosynthesis of archetypal plant self-defensive oxylipins by an endophytic fungus residing in mangrove embryos.

A trees travel companion: a fungal endophyte (Fusarium incarnatum) isolated from a viviparous propagule (embryo) of a mangrove tree produces typical plant defense oxylipins. Stable-isotope labeling experiments revealed that the endophyte biosynthesizes coriolic acid, didehydrocoriolic acid, and an epoxy fatty acid derived from linoleic acid by a process involving Δ(15)-desaturation and 13-lipoxygenation.

Synergistic activity of cosecreted natural products from amoebae-associated bacteria

Significance Bacterially produced small molecules are indispensable leads in the development of antibiotics, anticancer therapeutics, or immunomodulators. To unveil novel aspects in the biosynthetic potential of bacteria, a consideration of the ecological context in which the adapted producers thrive is extremely insightful. Here, we describe two natural products produced by Pseudomonas sp. QS1027, a bacterium that resides in the vicinity of the bacterial predator Dictyostelium discoideum. The two metabolites are jessenipeptin, a nonribosomal cyclic lipopeptide, and mupirocin, a known polyketide antibiotic. Both compounds are quorum-sensing regulated and display potent synergistic inhibitory activity against clinically relevant methicillin-resistant Staphylococcus aureus (MRSA). Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator–prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium discoideum. Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant Staphylococcus aureus, when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.

Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans

We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.