Deciphering the Timing of Naphthalenic Ring Formation in the Biosynthesis of 8-Deoxyrifamycins.

Although the biosynthesis of rifamycin has been studied for three decades, the biosynthetic formation of the naphthalenic ring remains unclear. In this study, by deletion of all post-PKS modification genes, we identified macrolactam precursors released from PKS. Isolated prorifamycins ( and ) have a benzenic chromophore and exist in two sets of macrocyclic atropisomers. The transformation from prorifamycins to benzenoid () and naphthalenoid () was suggested to be a non-enzymatic process, which is an off-PKS assembly.