Cofactor‐Free, Direct Photoactivation of Enoate Reductases for the Asymmetric Reduction of C=C Bonds

• Published in: Angewandte Chemie International Edition Vol. 56; no. 30; pp. 8681 - 8685
• Main Authors: Lee, Sahng Ha, Choi, Da Som, Pesic, Milja, Lee, Yang Woo, Paul, Caroline E., Hollmann, Frank, Park, Chan Beum
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17.07.2017; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: asymmetric reduction; Bonding; Cofactors; Communication; Communications; Continuity (mathematics); Conversion; Diodes; Dyes; Electrochemistry; Enantiomers; enoate reductases; Enzymes; Flavin; green chemistry; Hydrogenation; Illumination; Methylcyclohexanones; NAD; NADH; Nicotinamide; Nicotinamide adenine dinucleotide; Photoactivation; photocatalysis; Photochemistry; Photoreduction; Prostheses; redox enzymes; Reductases; Reduction; Spectroscopic analysis; White light; Xanthene; asymmetric reduction; photocatalysis; enoate reductases; green chemistry; redox enzymes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201702461

Enoate reductases from the family of old yellow enzymes (OYEs) can catalyze stereoselective trans‐hydrogenation of activated C=C bonds. Their application is limited by the necessity for a continuous supply of redox equivalents such as nicotinamide cofactors [NAD(P)H]. Visible light‐driven activation of OYEs through NAD(P)H‐free, direct transfer of photoexcited electrons from xanthene dyes to the prosthetic flavin moiety is reported. Spectroscopic and electrochemical analyses verified spontaneous association of rose bengal and its derivatives with OYEs. Illumination of a white light‐emitting‐diode triggered photoreduction of OYEs by xanthene dyes, which facilitated the enantioselective reduction of C=C bonds in the absence of NADH. The photoenzymatic conversion of 2‐methylcyclohexenone resulted in enantiopure (ee>99 %) (R)‐2‐methylcyclohexanone with conversion yields as high as 80–90 %. The turnover frequency was significantly affected by the substitution of halogen atoms in xanthene dyes. Flavin‐containing old yellow enzymes (OYE) are activated by molecular photosensitizers through direct transfer of photoinduced electrons to the prosthetic flavin moiety without any NAD(P)H cofactor. Rose bengal (4,5,6,7‐tetrachloro‐2′,4′,5′,7′‐tetraiodofluorescein, RB) and its xanthene derivatives are explored as photosensitizers to drive OYE‐catalyzed reduction of conjugated C=C bonds under visible light illumination.