Progress and Opportunities in Photochemical Enzymology of Oxidoreductases

Abstract

The mechanistic enzymology of oxidoreductases has contributed to the development of therapeutics, biomimetic synthetic catalysts, and engineered enzymes with improved or emergent function. Acquiring the atomic detail of an oxidoreductase’s mechanism is challenging, however, as the reaction coordinate is generally complex and the chemical steps of interest are often kinetically obscured. Recently, photosynthesis-inspired strategies have been applied to rapidly initiate oxidoreductase catalysis with light for mechanistic investigations, namely, the chemical potential jump (μ-jump) method and the design of artificially photosynthetic enzymes. While these methods are commonplace in (bio)photocatalysis, they are less frequently leveraged to gain insight into the oxidoreductase function. When paired with the appropriate spectroscopic tools to follow the ensuing events, such rapid initiation strategies enable the observation of chemical steps on time scales inaccessible by conventional mixing techniques. This Perspective summarizes the contributions of rapid initiation strategies to the mechanistic understanding of hydrogenases and artificially photosynthetic ribonucleotide reductases. Opportunities in other oxidoreductases are discussed.