Metabolic Blockade-Based Genome Mining of <i>Malbranchea circinata</i> SDU050: Discovery of Diverse Secondary Metabolites
Hu Yang | Xiaowei Luo | Zhuo Shang | Kunlong Li | Jian Cai | Yingying Chen | Longchao Xin | Jianhua Ju
<i>Malbranchea circinata</i> 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 <i>M. circinata</i> SDU050, alongside five additional metabolite classes, including three novel cytochalasins (<b>7</b>–<b>9</b>), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (<b>1</b>) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (<b>1</b>) and (−)-mycousnine (<b>10</b>) exhibited weak antibacterial activity against Gram-positive bacteria such as <i>Staphylococcus aureus</i>, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and <i>Bacillus subtilis</i>. These findings underscore the chemical diversity and biosynthetic potential of <i>M. circinata</i> SDU050 and highlight an effective strategy for exploring marine fungal metabolites.
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