Nonenzymatic and Metal-Free Organocatalysis for in Situ Regeneration of Oxidized Cofactors by Activation and Reduction of Molecular Oxygen

Abstract

The application of synthetic flavinium organocatalysts for the in situ regeneration of oxidized cofactors NAD­(P)+ using O2 as the terminal oxidant without any special illumination or equipment is reported. With the aid of the highly active bridged flavinium catalyst, the rate of NAD­(P)H oxidation is accelerated by 3 orders of magnitude. The results show that the catalytic activity of the bridged flavinium catalyst is not dependent on light but on only oxygen. Furthermore, this catalyst is compatible with various preparative enzymatic oxidation reactions. A hydride transfer mechanism is proposed for the presented system.

Regulating Cofactor Balance In Vivo with a Synthetic Flavin Analogue

“…Recently, sugars like d ‐mannose have been getting increasing attention for health care and pharmaceutical interests due to its potential biological activities . As shown in the Scheme , SBFA were efficient for aerobic NAD + regeneration in vitro, and the order of catalytic activity of these SBFA appeared to be F1 > F2 > F4 > F3 , which agrees well with our previous reports . In the presence of 0.1 mol % F1 and 2 mol % NAD + , the desired product mannose was obtained in 81 % yield in 24 h. Control experiments ruled out the possibility of direct oxidation of the substrate by the SBFA.…”

“…Recently, we reported the feasibility of using synthetic bridged flavin analogue (SBFA) for the NAD(P) + regeneration in vitro . It appeared that further ionization modification of the structure of SBFA might enhance its uptake by cells through free diffusion, thereby establishing a new artificial system to manipulate cofactor balance in vivo without modifying the cell membrane.…”

Regulating Cofactor Balance In Vivo with a Synthetic Flavin Analogue

“…[13] As shown in the Scheme 1, SBFAwere efficient for aerobic NAD + regeneration in vitro, and the order of catalytic activity of these SBFAappeared to be F1 > F2 > F4 > F3,w hich agrees well with our previous reports. [12] In the presence of 0.1 mol % F1 and 2mol % NAD + ,t he desired product mannose was obtained in 81 % yield in 24 h. Control experiments ruled out the possibility of direct oxidation of the substrate by the SBFA. Under these nonoptimized conditions,t he calculated turnover frequency (TOF) of F1 was 33.8 h À1 ,w hich is 10-fold higher than that catalyzed by the natural flavin FMN (3.3 h À1 ), thus indicating Scheme 1.…”

“…[12] It appeared that further ionization modification of the structure of SBFAm ight enhance its uptake by cells through free diffusion, thereby establishing an ew artificial system to manipulate cofactor balance in vivo without modifying the cell membrane.S uch as ynthetic flavin analogue system, which has not been reported so far to the best of our knowledge,was examined with E. coli to enhance intracellular nicotinamide cofactor recycling for whole-cell biocatalysis. [12] It appeared that further ionization modification of the structure of SBFAm ight enhance its uptake by cells through free diffusion, thereby establishing an ew artificial system to manipulate cofactor balance in vivo without modifying the cell membrane.S uch as ynthetic flavin analogue system, which has not been reported so far to the best of our knowledge,was examined with E. coli to enhance intracellular nicotinamide cofactor recycling for whole-cell biocatalysis.…”

“…Recently,w er eported the feasibility of using synthetic bridged flavin analogue (SBFA) for the NAD(P) + regeneration in vitro. [12] It appeared that further ionization modification of the structure of SBFAm ight enhance its uptake by cells through free diffusion, thereby establishing an ew artificial system to manipulate cofactor balance in vivo without modifying the cell membrane.S uch as ynthetic flavin analogue system, which has not been reported so far to the best of our knowledge,was examined with E. coli to enhance intracellular nicotinamide cofactor recycling for whole-cell biocatalysis.…”