Discovering and harnessing oxidative enzymes for chemoenzymatic synthesis and diversification of anticancer camptothecin analogues

Abstract

Camptothecin derivatives are precursors of potent anticancer agents, but their biosynthesis remains largely unknown. Here two cytochrome P450 monooxygenases are shown to regiospecifically oxidize camptothecin, yielding 10- and 11- hydroxylated derivatives, which are subsequently used to produce a suite of known anticancer drugs and derivatives.