Genome-based mining of new antimicrobial meroterpenoids from the phytopathogenic fungus Bipolaris sorokiniana strain 11134

Polyketide–terpenoid hybrid compounds are one of the largest families of meroterpenoids, with great potential for drug development for resistant pathogens. Genome sequence analysis of secondary metabolite gene clusters of a phytopathogenic fungus, Bipolaris sorokiniana 11134, revealed a type I polyketide gene cluster, consisting of highly reducing polyketide synthase, non-reducing polyketide synthase, and adjacent prenyltransferase. MS- and UV-guided isolations led to the isolation of ten meroterpenoids, including two new compounds: 19-dehydroxyl-3- epi -arthripenoid A ( 1 ) and 12-keto-cochlioquinone A ( 2 ). The structures of 1 – 10 were elucidated by the analysis of NMR and high-resolution electrospray ionization mass spectroscopy data. Compounds 5 – 8 and 10 showed moderate activity against common Staphylococcus aureus and methicillin-resistant S. aureus , with minimum inhibitory concentration (MIC) values of 12.5–100 μg/mL. Compound 5 also exhibited activity against four clinical resistant S. aureus strains and synergistic antifungal activity against Candida albicans with MIC values of 12.5–25 μg/mL. The biosynthetic gene cluster of the isolated compounds and their putative biosynthetic pathway are also proposed. Key Points • Ten meroterpenoids were identified from B. sorokiniana, including two new compounds. • Cochlioquinone B ( 5 ) showed activity against MRSA and synergistic activity against C. albicans. • The biosynthetic gene cluster and biosynthetic pathway of meroterpenoids are proposed. • Genome mining provided a new direction to uncover the diversity of meroterpenoids.