Characterization of the Glycosyltransferase and Methyltransferase Encoded Remotely from the Actinopyrone Biosynthetic Gene Cluster Enables Access to Diverse Analogues

The actinopyrone biosynthetic gene cluster () lacks glycosyl- and methyltransferase genes, yet its product clearly calls for such enzymes. Using bioinformatics and biochemical methods, we confirmed that the and genes, well beyond the cluster boundaries, encode methyltransferase and glycosyltransferase, respectively. Moreover, homologous protein GT1507 enabled us to produce 14 non-natural actinopyrone analogues. PM050463 () was found to display potent anti- activity and no signs of cytotoxicity.