Synergistic activity of cosecreted natural products from amoebae-associated bacteria.

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.

Iron-Catalyzed Cross-Coupling of Alkenyl Acetates.

Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1-2 mol%).

Structure elucidation of the syringafactin lipopeptides provides insight in the evolution of nonribosomal peptide synthetases.

Modular biosynthetic machineries such as polyketide synthases (PKSs) or nonribosomal peptide synthetases (NRPSs) give rise to a vast structural diversity of bioactive metabolites indispensable in the treatment of cancer or infectious diseases. Here, we provide evidence for different evolutionary processes leading to the diversification of modular NRPSs and thus, their respective products. Discovery of a novel lipo-octapeptide family from Pseudomonas, the virginiafactins, and detailed structure elucidation of closely related peptides, the cichofactins and syringafactins, allowed retracing recombinational diversification of the respective NRPS genes. Bioinformatics analyses allowed us to spot an evolutionary snapshot of these processes, where recombination occurred both within the same and between different biosynthetic gene clusters. Our systems feature a recent diversification process, which may represent a typical paradigm to variations in modular biosynthetic machineries.

Rationalizing the Right Ratios.

The three hydroxamate siderophores, avaroferrin, bisucaberin, and putrebactin are synthesized by the same key enzyme AvbD. Rütschlin et al. (2017) show that the ratio of these three compounds is not governed by the enzyme's substrate specificity but rather by the substrate pool. This ensures a large metabolic flexibility and adaptability to new environments.