(438b) Development of a Novel Cooperative Photoenzymatic System for Stereoconvergent Reduction of C=C without Co-Factor Regeneration

Living organisms rely on simultaneous reactions that are catalyzed by mutually compatible and selective enzymes to synthesize metabolites in an energy efficient manner. To combine the advantages of biocatalysis with chemocatalysis, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and chemical catalysts. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained from the two reactions run sequentially with their respective substrates, which makes them particularly valuable. However, such reactions are difficult to develop due to mutual inactivation and distinct reaction conditions between chemical catalysts and biocatalysts. We previously reported a new class of cooperative chemoenzymatic reactions that combine photocatalysts that isomerize alkenes with ene-reductases that selectively reduce C=C of one isomer to generate valuable enantioenriched products. This system is limited by the necessity of a continuous supply of expensive, none-stable redox nicotinamide cofactor NADPH. In this study, we successfully integrated visible light-driven direct electron transfer process in our previous system to stereoconvergently reduce an E/Z mixture of alkenes without using NADPH. In this novel cooperative photoenzymatic system, photocatalyst-catalyzed alkene isomerization worked cooperatively with light-driven ene-reductases activation and selective enzymatic reduction without mutual inactivation. The system affords a range of enantioenriched precursors to biologically active compounds.