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

Autor: Han, Jianying, Zhang, Jingyu, Song, Zhijun, Zhu, Guoliang, Liu, Miaomiao, Dai, Huanqin, Hsiang, Tom, Liu, Xueting, Zhang, Lixin, Quinn, Ronald J, Feng, Yunjiang
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Zdroj: Applied Microbiology & Biotechnology; May2020, Vol. 104 Issue 9, p3835-3846, 12p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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