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A Correlative Metabologenomics Approach for the Discovery of Specialized Metabolites in Marine Fungi

Secondary or specialized metabolites (SMs) remain the most important source of drug leads. Research in the last decades highlights the great genetic potential and increasing importance of fungi for finding bioactive and novel SMs. However, this potential is far from being exhausted, especially, SMs from understudied sources like marine-derived fungi. The main reasons are limited sequencing data for the latter and the presence of cryptic/silent genes, potentially making up 90% of all biosynthetic gene clusters (BGCs). To fill this gap and to unravel SMs as well as their genetic potential, we plan to sequence the genomes and analyze transcriptomes of less studied strains, 38 Phoma and 12 Acremonium, from diverse ecological marine niches and locations, which are mostly associated with other organisms like sponges and macroalgae. We expect to find novel bioactive SMs, intriguing enzymes and catalyzed reactions from these strains.

Selected marine Phoma sp. from diverse ecological niches.

Meanwhile, the genome sequences are also important for other research fields, e.g. studying on their relationships to hosts and environments. Correlative metabologenomics allows the comparison of fungal metabolites produced with the predicted biosynthetic gene clusters from the associated genome. Therefore, known natural products will be detected from LC/MS data and clustered and dereplicated using the GNPS framework with its integrated database. The compounds will then be further investigated using in-silico frameworks such as SIRIUS. Fungal BGCs will be identified by fungiSMASH and clustered by BiG-SCAPE using the MIBiG database for annotation of known BGCs. 

Recently, we developed a MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides from the marine sponge-derived fungus Stachylidium bicolor 293 K04.

These projects are investigated by Bastian Brand and Tim Berger.