Is Simpler Better? Synthetic Nicotinamide Cofactor Analogues for Redox Chemistry

Abstract

The topic of synthetic nicotinamide cofactor analogues is resurfacing as new approaches are being explored, especially in the areas of organic chemistry and biocatalysis. By changing the adenine dinucleotide moiety for a simpler alkyl or aryl group and taking advantage of their ability for hydride transfer, these cofactor biomimetics are used in redox reactions in catalytic or stoichiometric amounts. Alteration of the amide functional group on the pyridine ring, thus varying their electronic properties, and the presence of divalent metal ions also enable rate acceleration in enzyme-catalyzed and chemical reactions. Herein, an overview of the synthesis, mechanism, and applications of nicotinamide cofactor NAD(P)H analogues in redox chemistry, particularly 1,4-dihydronicotinamide derivatives and their oxidized counterpart, is presented. These compounds have been extensively studied as models of NAD(P)H for enzymatic reactions with oxidoreductases as well as nonenzymatic reactions, and the focus of this review is placed mainly on the scope and limitations of these synthetic analogues in biocatalysis.

New artificial fluoro-cofactor of hydride transfer with novel fluorescence assay for redox biocatalysis

“…4 NAD(P) contain two parts, the nicotinamide moiety acting as a hydride donor or acceptor and the adenine dinucleotide moiety playing an important role in separating between the anabolic and catabolic pathways. 5 Although the anabolic and catabolic pathways are necessary for survival, it is not essential to realize hydride transfer in redox biocatalysis. Hence a number of nicotinamide-containing artificial cofactors have been reported (Fig.…”

“…5 In order to lower its reducing potential, much focus has been emphasized on the structure modification and scaffold hopping of the 1,4-dihydropyridine skeleton (Fig. 2).…”

Performance of Recombinant‐Whole‐Cell‐Catalyzed Reductions in Deep‐Eutectic‐Solvent–Aqueous‐Media Mixtures

“…[1] In this respect, the set-up of highly efficient and creative cofactor regeneration systems has been sorted out with outstanding results so far, comprising both free, isolated enzymes, and whole-cells, 2] as well as natural and non-natural cofactors. [3] Likewise, different concepts related to medium engineering -e.g. use of organic co-solvents or biphasic systems to enhance substrate loadings -have been in-depth assessed as well.…”

“…solvent-free or organic solvents), thus enabling biocatalytic oxidoreductions in non-conventional media, and opening new possibilities for these enzymes. [2][3][4] Last but not least, the identification of novel useful catalytic performances for these biocatalysts -e.g. imine reductases [5] -, provides even a stronger potential for future sustainable solutions in enzyme catalysis.…”

High-yield hydrogen production from biomass by in vitro metabolic engineering: Mixed sugars coutilization and kinetic modeling

“…These include replacing the expensive and labile cofactor NADP + with a cheap and stable biomimetic, replacing key unstable enzymes (e.g., PPGK, PGM), using cheap and abundant substrates, and achieving hydrogen production at high rate and yield. The first two challenges, use of biomimetic cofactors and improving enzyme stability, may be addressed through the discovery of more thermoenzymes, enzyme engineering, and immobilization (16,35). This study has addressed the latter two challenges, using cheap biomass sugars in a high-yield reaction and increasing the volumetric productivity.…”