Expanding the Chemical Diversity of Fasamycin Via Genome Mining and Biocatalysis.

Genome mining and biocatalytic modification of chemical structures are critical methods to develop new antibiotics. In this study, eight new fasamycins (, , , and -) along with five known analogues (, , , , and ) were obtained by the overexpression of two phosphopantetheinyl transferases (PPtases) in and biocatalytic transformation with two halogenases. These new compounds displayed significant activity against and , in particular, C-29-methyl and C-2/C-22-halogen derivatives. This study increases the chemical diversity of bioactive fasamycin derivatives and provides useful halogenation tools for engineering their scaffolds.