Characterization of Tailoring Methyltransferases Involved in K-41A Biosynthesis: Modulating Methylation to Improve K-41A Anti-infective Activity.

Jiang Chen, Chun Gui, Qiuyu Wei, Jie Liu, Li Ye, Xinpeng Tian, Yu-Cheng Gu, Qinglian Li, Jianhua Ju

Organic letters 2020 Jun 19

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The biosynthetic gene cluster (BGC) for polyether antibiotic K-41A was identified from marine-derived Streptomyces sp. SCSIO 01680 and subjected to combinatorial biosynthetic study. Bioinformatics analyses, gene disruption, and metabolomics analyses afforded eight new derivatives and one known polyether, showcasing five region-specific methyltransferases Pak13, Pak15, Pak20, Pak31, and Pak38 and their respective modification loci. Moreover, bioassays revealed that two disaccharide-bearing polyethers, K-41B and K-41Bm, display enhanced anti-HIV and potent antibacterial activities.

Citation

Jiang Chen, Chun Gui, Qiuyu Wei, Jie Liu, Li Ye, Xinpeng Tian, Yu-Cheng Gu, Qinglian Li, Jianhua Ju. Characterization of Tailoring Methyltransferases Involved in K-41A Biosynthesis: Modulating Methylation to Improve K-41A Anti-infective Activity. Organic letters. 2020 Jun 19;22(12):4627-4632