Stepwise cyclopropanation on the polycyclopropanated polyketide formation in jawsamycin biosynthesis

Jawsamycin is a polyketide-nucleoside hybrid with a unique poly-cyclopropane moiety on a single polyketide chain. The unexpected isolation of cyclopropane deficient jawsamycin analogs allowed us to propose a stepwise cyclopropanation mechanism for the enzymatic synthesis of this polyketide. The concise timing of the cyclopropanation could be regulated by a delicate balance between reaction rates of the condensation and cyclopropanation reactions.