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Morphotype switches frequently occur in Actinobacteria and are often associated with disparate natural product production. Here, we report on differences in the secondary metabolomes of two morphotypes of a

Here, we report the isolation and characterization of three new spirocyclic natural products named cladosporicin A (1), cladosporiumins I (2) and J (3) from the fungus Cladosporium sphaerospermum SW67. Cladosporicin A contains an unprecedented 2,7-diazaspiro[4.5]decane-1,4-dione skeleton conjugated with one 2,4-pyrrolidinedione moiety (tetramic acid). Cladosporiumins I and J are stereoisomers and are built of a tetramic acid core structure with a quaternary (C-3) center carrying a trans-hexylenic alcohol side chain and a six-membered lactone ring. The absolute structures of compounds 1–3 were elucidated by a combination of 1D and 2D NMR spectroscopy, modified Mosher's analysis, quantum chemical ECD calculations and computational NMR chemical shift calculations. Comparative genome sequence analysis led us to assign the putative new PKS-NRPS hybrid gene cluster (cls). Finally, we assessed bioactivities of compounds 1–3 in a series of pharmacological tests and found weak cytotoxicity against four human breast cancer cell lines (IC50 ∼ 70–90 μM).

Morphotype switches frequently occur in Actinobacteria and are often associated with disparate natural product production. Here, we report on differences in the secondary metabolomes of two morphotypes of a Streptomyces species, including the discovery of a novel antimicrobial glycosylated macrolide, which we named termidomycin A. While exhibiting an unusual 46-member polyene backbone, termidomycin A (1) shares structural features with the clinically important antifungal agents amphotericin B and nystatin A1. Genomic analyses revealed a biosynthetic gene cluster encoding for a putative giant type I polyketide synthase (PKS), whose domain structure allowed us to propose the relative configuration of the 46-member macrolide. The architecture of the biosynthetic gene cluster was different in both morphotypes, thus leading to diversification of the product spectrum. Given the high frequency of genomic rearrangements in Streptomycetes, the metabolic analysis of distinct morphotypes as exemplified in this study is a promising approach for the discovery of bioactive natural products and pathways of diversification.

Despite the wealth of physiological knowledge and plentiful genomes available, only few natural products of anaerobic bacteria have been identified until today and even less have been linked to their biosynthetic gene cluster. Here, we analyzed a unique NRPS-PKS hybrid gene cluster from an anaerobic Epsilonproteobacterium ( Sulfurospirillum barnesii). Phylogenetic analysis of key biosynthetic genes, gene expression studies, and comparative metabolomics resulted in the identification of the first anoxically biosynthesized NRPS-PKS hybrid metabolite: a lipo-dipeptide with a vinylogous side chain, called barnesin A. The absolute structure was verified by a modular total synthesis, and barnesin and derivatives were found to have antimicrobial activity, as well as selective and nanomolar inhibitory activity, against pharmacological important cysteine proteases, such as cathepsin B.

The chemical analysis of bacteria-induced morphogenesis of marine microeukaryotes and invertebrates is of fundamental importance and provides insight into metazoan evolution and the origins of morphological complexity. In only few cases the morphogenesis-inducing bacteria could be characterized and the responsible signalling molecules identified. Using defined model systems of cross-kingdom interactions is essential to dissect the molecular mechanisms and chemical signals involved.

Five hybrid polyketides (1a, 1b, and 2−4) containing tetramic acid core including a new hybrid polyketide, cladosin L (1), were isolated from the marine fungus Cladosporium sphaerospermum SW67, which was isolated from the marine hydroid polyp of Hydractinia echinata. The hybrid polyketides were isolated as a pair of interconverting geometric isomers. The structure of 1 was determined based on 1D and 2D NMR spectroscopic and HR-ESIMS analyses. Its absolute configuration was established by quantum chemical electronic circular dichroism (ECD) calculations and modified Mosher’s method. Tetramic acid-containing compounds are reported to be derived from a hybrid PKS-NRPS, which was also proved by analyzing our 13C-labeling data. We investigated whether compounds 1−4 could prevent cell damage induced by cisplatin, a platinum-based anticancer drug, in LLC-PK1 cells. Co-treatment with 2 and 3 ameliorated the damage of LLC-PK1 cells induced by 25 μM of cisplatin. In particular, the effect of compound 2 at 100 μM (cell viability, 90.68 ± 0.81%) was similar to the recovered cell viability of 88.23 ± 0.25% with 500 μM N-acetylcysteine (NAC), a positive control.

Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We demonstrate that the exploration of specific microbial–host interactions, in combination with multidisciplinary dereplication processes, has emerged as a successful strategy to identify novel chemical entities and to shed light on the ecology and evolution of defensive associations.

Illumina 16S rRNA gene sequencing was used to profile the associated bacterial community of the marine hydroid Hydractinia echinata, a long-standing model system in developmental biology. 56 associated bacteria were isolated and evaluated for their antimicrobial activity. Three strains were selected for further in-depth chemical analysis leading to the identification of 17 natural products. Several γ-Proteobacteria were found to induce settlement of the motile larvae, but only six isolates induced the metamorphosis to the primary polyp stage within 24 h. Our study paves the way to better understand how bacterial partners contribute to protection, homeostasis and propagation of the hydroid polyp.

Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We demonstrate that the exploration of specific microbial–host interactions, in combination with multidisciplinary dereplication processes, has emerged as a successful strategy to identify novel chemical entities and to shed light on the ecology and evolution of defensive associations.

The assembly and annotation of the draft genome sequence of Shewanella sp. strain P1-14-1 are reported here to investigate the genes responsible for interkingdom interactions, secondary metabolite production, and microbial electrogenesis.

The genomes of three Pseudoalteromonas strains (P1-8, P1-11, and P1-30) were sequenced and assembled. These genomes will inform future study of the genes responsible for the production of biologically active compounds responsible for these strains’ antimicrobial, biofouling, and algicidal activities.

Bacterial biofilms profoundly influence the recruitment and settlement of marine invertebrates, critical steps for diverse marine processes such as coral reef formation, marine fisheries and the fouling of submerged surfaces. Yet, the complex composition of biofilms often makes it challenging to characterize the individual signals and regulatory mechanisms. SI material contains details on fermentation, cultivation, sample treatment, bioassays, isolation procedures, ESI-HRMS, 1H NMR, 13C NMR, and 2D NMR spectra as well as additional assay data.