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

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, Pak1S, 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.