Abstract
Halogen substituents are important for biological activity in many compounds. Genome-based mining of halogenase along with its biosynthetic gene cluster provided an efficient approach for the discovery of naturally occurring organohalogen compounds. Analysis of the genome sequence of a phytopathogenic fungus Bipolaris sorokiniana 11134 revealed a polyketide gene cluster adjacent to a flavin-dependent halogenase capable of encoding halogenated polyketides, which are rarely reported in phytopathogenic fungi. Furthermore, MS- and UV-guided isolation and purification led to the identification of five chlorine-containing natural products together with seven other chromones and xanthones. Two of the chlorinated compounds and four chromones are new compounds. Their structures were elucidated by NMR spectroscopic analysis and HRESIMS data. The biosynthetic gene clusters of isolated compounds and their putative biosynthetic pathway are also proposed. One new chlorinated compound showed activity against Staphylococcus aureus, methicillin-resistant S. aureus, and three clinical-resistant S. aureus strains with a shared minimum inhibitory concentration (MIC) of 12.5 μg/mL. Genome-based mining of halogenases combined with high-resolution MS- and UV-guided identification provides an efficient approach to discover new halogenated natural products from microorganisms.
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Funding
This work was supported by grants from the National Natural Science Foundation of China (31430002, 81573341, 21877038, 31720103901, 31320103911), Open Project Funding of the State Key Laboratory of Bioreactor Engineering, the 111 Project (B18022), the Fundamental Research Funds for the Central Universities (22221818014), the Natural Science Foundation from Shandong Province (No. ZR2017ZB0206), and Taishan Scholarship. The authors acknowledge the Australian Research Council (ARC) for support (LE140100119, LE20100170). J. Han thanks the Griffith University for the provision of the Ph.D. scholarships (GUPRS and GUIPRS). Genome sequencing and assembly of BS11134 were supported by funding from the Natural Science and Engineering Research Council of Canada to T. Hsiang.
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Han, J., Zhang, J., Song, Z. et al. Genome- and MS-based mining of antibacterial chlorinated chromones and xanthones from the phytopathogenic fungus Bipolaris sorokiniana strain 11134. Appl Microbiol Biotechnol 103, 5167–5181 (2019). https://doi.org/10.1007/s00253-019-09821-z
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DOI: https://doi.org/10.1007/s00253-019-09821-z