Genome Mining Guided Discovery of Macrocyclic Sesterterpenoids with Anti-MRSA and Anti-Neuroinflammatory Activities #MMPMID41391173
Lan K; Wang Z; Lv K; Xing C; Li X; Yin Q; Chen Y; Mo X; Mao X; Wu W; Hsiang T; Zhang L; Dai H; Liu X; Zhu G; Jiang L
J Agric Food Chem 2025[Dec]; ? (?): ? PMID41391173show ga
Terpenoids exhibit antioxidant, antimicrobial, and health-promoting activities, and are widely utilized in the food industry. In this study, a new bifunctional terpene synthase (BFTPS) and its associated gene cluster were identified in Colletotrichum cereale 00173 through a genome mining approach. Heterologous expression of the BFTPS and its gene cluster in Aspergillus oryzae NSAR1 led to the production of a 14-membered macrocyclic sesterterpene, colcerepene (1), and four hydroxylated derivatives, colcerepenoids A-D (2-5). The biosynthetic pathway of compounds 1-5 was further elucidated through feeding experiments. Notably, compound 1 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an MIC value of 6.25 muM. This study is the first report of anti-MRSA activity in macrocyclic sesterterpenoids, expanding the functional space of macrocyclic sesterterpenoids as promising leads for developing agents against foodborne pathogens.
J+Agric+Food+Chem 2025 ; ? (?): ?
