Pyridoxal photoenzymes for asymmetric radical-radical cross-couplings.

Not reported in abstract.

Summary and findings

Not reported in abstract.

Abstract

Non-native photoenzymes have enabled myriad asymmetric bond-forming events that are otherwise challenging or at present impossible with small-molecule catalysis1,2. These reactions require enzymes with cofactors that are strong absorbers in the visible region with reasonably long-lived excited states, such as flavin and nicotinamide. However, there exists a substantial chromophoric cofactor 'dark space' in which no known photoenzymatic activity has been characterized1. Increased knowledge of the photophysics of the cofactors in the 'dark space' would increase the types of bonds that photoenzymes can form by accessing new excited-state intermediates in enzyme classes with divergent reactivities and selectivities. Here, we establish pyridoxal 5'-phosphate (PLP) as a photoenzymatic cofactor by leveraging the excited-state quinonoid intermediate as a potent single-electron reductant. We overcome the poor photophysical properties of the native quinonoid intermediate by using non-native benzylamine substrates and exploiting Förster resonance energy transfer mechanism from an exogenous photosensitizer to access the quinonoid excited state. This redox neutral approach enables an asymmetric radical-radical cross-coupling between benzylamines and reductive radical precursors through concomitant generation and localization of a radical pair in an enzyme active site-overcoming the typical challenges associated with this reaction by removing the necessity for radical sorting and the persistent radical effect3. The emergent photoexcited intermediates of PLP identified in this work greatly expand the potential avenues for valuable bond-forming events by PLP-dependent enzymes.

Limitations

Not reported in abstract.

Elsewhere in the NAD+ (Nicotinamide Adenine Dinucleotide) corpus