Light-Driven Deracemization by a Designed Photoenzyme

Abstract

The creation of enzymes with abiological abilities offers exciting opportunities to access new-to-nature biocatalysis beyond that found in nature. Here, we repurpose a novel protein scaffold, CTB10, as an artificial photoenzyme through genetic code expansion. It enables catalytic deracemization of cyclopropane, a process that remains inaccessible to traditional biocatalysis due to its thermodynamically unfavorable nature. Following structural optimization through directed evolution, a broad substrate scope with high enantioselectivities is achieved. Furthermore, the crystal structure of the CTB10-based photoenzyme–substrate complex well demonstrates how the catalytic chiral cavity is sculpted to promote efficient and selective light-enabled deracemization. Therefore, this study unlocks the potential for achieving challenging deracemization through biocatalysis.