ALBERT

Description: Sea foam harbors a diverse range of fungal spores with biological and ecological relevance in marine environments. Fungi are known as the producers of secondary metabolites that are used in health and agricultural sectors, however the potentials of sea foam-derived fungi have remained unexplored. In this study, organic extracts of six foam-derived fungal isolates belonging to the genera Penicillium, Cladosporium, Emericellopsis and Plectosphaerella were investigated for their antimicrobial activity against plant and human pathogens and anticancer activity. In parallel, an untargeted metabolomics study using UPLC-QToF–MS/MS-based molecular networking (MN) was performed to unlock their chemical inventory. Penicillium strains were identified as the most prolific producers of compounds with an average of 165 parent ions per strain. In total, 49 known mycotoxins and functional metabolites were annotated to specific and ubiquitous parent ions, revealing considerable chemical diversity. This allowed the identification of putative new derivatives, such as a new analog of the antimicrobial tetrapeptide, fungisporin. Regarding bioactivity, the Penicillium sp. isolate 31.68F1B showed a strong and broad-spectrum activity against seven plant and human pathogens, with the phytopathogen Magnaporthe oryzae and the human pathogen Candida albicans being the most susceptible (IC50 values 2.2 and 6.3 µg/mL, respectively). This is the first study mining the metabolome of the sea foam-derived fungi by MS/MS-based molecular networking, and assessing their biological activities against phytopathogens.

Description: Microbial co-cultivation is employed for awakening silent biosynthetic gene clusters (BGCs) to enhance chemical diversity. However, the selection of appropriate partners for co-cultivation remains a challenge. Furthermore, competitive interactions involving the suppression of BGCs or upregulation of known, functional metabolite(s) during co-cultivation efforts is also common. Herein, we performed an alternative approach for targeted selection of the best co-cultivation pair. Eight marine sediment-derived fungi were classified as strong or weak, based on their anti-phytopathogenic potency. The fungi were co-cultured systematically and analyzed for their chemical profiles and anti-phytopathogenic activity. Based on enhanced bioactivity and a significantly different metabolite profile including the appearance of a co-culture specific cluster, the co-culture of Plenodomus influorescens (strong) and Pyrenochaeta nobilis (weak) was prioritized for chemical investigation. Large-scale co-cultivation resulted in isolation of five polyketide type compounds: two 12-membered macrolides, dendrodolide E (1) and its new analog dendrodolide N (2), as well as two rare azaphilones spiciferinone (3) and its new analog 8a-hydroxy-spiciferinone (4). A well-known bis-naphtho-γ-pyrone type mycotoxin, cephalochromin (5), whose production was specifically enhanced in the co-culture, was also isolated. Chemical structures of compounds 1–5 were elucidated by NMR, HRMS and [α] D 20 analyses. Compound 5 showed the strongest anti-phytopathogenic activity against Xanthomonas campestris and Phytophthora infestans with IC50 values of 0.9 and 1.7 µg/mL, respectively.

Description: It is widely accepted that the commensal gut microbiota contributes to the health and well-being of its host. The solitary tunicate Ciona intestinalis emerges as a model organism for studying host–microbe interactions taking place in the gut, however, the potential of its gut-associated microbiota for marine biodiscovery remains unexploited. In this study, we set out to investigate the diversity, chemical space, and pharmacological potential of the gut-associated microbiota of C. intestinalis collected from the Baltic and North Seas. In a culture-based approach, we isolated 61 bacterial and 40 fungal strains affiliated to 33 different microbial genera, indicating a rich and diverse gut microbiota dominated by Gammaproteobacteria. In vitro screening of the crude microbial extracts indicated their antibacterial (64% of extracts), anticancer (22%), and/or antifungal (11%) potential. Nine microbial crude extracts were prioritized for in-depth metabolome mining by a bioactivity- and chemical diversity-based selection procedure. UPLC-MS/MS-based metabolomics combining automated (feature-based molecular networking and in silico dereplication) and manual approaches significantly improved the annotation rates. A high chemical diversity was detected where peptides and polyketides were the predominant classes. Many compounds remained unknown, including two putatively novel lipopeptides produced by a Trichoderma sp. strain. This is the first study assessing the chemical and pharmacological profile of the cultivable gut microbiota of C. intestinalis.