Metabolic Blockade-Based Genome Mining of SDU050: Discovery of Diverse Secondary Metabolites.

SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type SDU050, alongside five additional metabolite classes, including three novel cytochalasins (-), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin () enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin () and (-)-mycousnine () exhibited weak antibacterial activity against Gram-positive bacteria such as , methicillin-resistant (MRSA), and . These findings underscore the chemical diversity and biosynthetic potential of SDU050 and highlight an effective strategy for exploring marine fungal metabolites.