Synthetische Nikotinamide in der Biokatalyse

Abstract

NIEDERLANDENatural nicotinamide cofactors (NAD(P)) can in some cases be replaced by simple synthetic analogues (mNADs). These analogues can enable 'faster than naturally designed' enzymatic reactions, more efficient reaction processes and more chemoselective reactions because of their bioorthogonality.ó Die Nikotinamidkofaktoren Nikotinamidadenindinukleotid (NAD) und Nikotinamidadenindinukleotidphosphat (NADP) sind die zentralen Redoxkoenzyme aller bekannten Lebewesen. Da sie für viele enzymatische Redoxreaktionen unabdingbar sind, spielen sie auch in der Biokatalyse eine wichtige Rolle. In den letzten Jahrzehnten lag ein Schwerpunkt in der Redoxbiokatalyse-Forschung auf der Entwicklung effizienter in situ-Regenerationssysteme, die einen katalytischen Einsatz von NAD(P) ermöglichen.

Old Yellow Enzyme-Catalysed Asymmetric Hydrogenation: Linking Family Roots with Improved Catalysis

“…A highly promising and elegant alternative is the use of relatively inexpensive nicotinamide coenzyme biomimetics (NCBs) [52][53][54][55][56]. The latter compounds retain the pyridine ring structure, substituted with varied functional groups either on the N1 nitrogen (NCBs 1-2, 6-7, Figure 1) or at the C3 carbon (NCBs 3-5) [55].…”

Alternative coenzymes for biocatalysis

“…Nevertheless, significant efforts are undertaken to develop simpler, more efficient alternatives [5,8]. Natural-based NADH analogues have been used to investigate the influence of substituents on the dihydropyridine ring, and synthetic nicotinamide coenzyme biomimetics (NCBs) were produced to investigate the hydride transfer mechanism, but more recently were attractive to provide inexpensive alternative coenzymes ( Figure 1) [5,[9][10][11].…”

Synthetic Biomimetic Coenzymes and Alcohol Dehydrogenases for Asymmetric Catalysis

“…Synthetic nicotinamide coenzyme biomimetics (NCBs) have been shown to replace NAD(P)H in flavin-dependent enzymes such as nitroreductase and NAD(P)H quinone oxidoreductase [5][6][7], a cytochrome P450 BM3 variant [8], ene-reductases [9][10][11][12][13][14][15][16], and styrene monooxygenase [17]. In all cases described, a flavin was involved as an electron mediator [18][19][20][21][22].…”

“…Synthetic nicotinamide coenzyme biomimetics (NCBs) have been shown to replace NAD(P)H in flavin-dependent enzymes such as nitroreductase and NAD(P)H quinone oxidoreductase [5-7], a cytochrome P450 BM3 variant [8], ene-reductases [9][10][11][12][13][14][15][16], and styrene monooxygenase [17]. In all cases described, a flavin was involved as an electron mediator [18][19][20][21][22].Jones pioneered the use of synthetic cofactor analogues with horse liver ADH (HLADH) [23][24][25][26], followed by Fish [27] and others [28,29]. A dehydrogenase from the aldo-reductase superfamily from Pyrococcus furiosus (AdhD) was engineered to increase catalytic efficiency towards nicotinamide mononucleotide (NMN, Figure 1A) [30,31].…”