1. Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites.
- Author
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Yang H, Luo X, Shang Z, Li K, Cai J, Chen Y, Xin L, and Ju J
- Subjects
- Polyketide Synthases genetics, Biosynthetic Pathways genetics, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus genetics, Geologic Sediments microbiology, Isocoumarins pharmacology, Isocoumarins chemistry, Genome, Fungal, Microbial Sensitivity Tests, Secondary Metabolism, Anti-Bacterial Agents pharmacology, Multigene Family
- Abstract
Malbranchea circinata 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 M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins ( 7 - 9 ), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin ( 1 ) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin ( 1 ) and (-)-mycousnine ( 10 ) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus , methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis . These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites.
- Published
- 2025
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