Catalytic mechanism and application of formate dehydrogenase

Abstract

NAD+-dependent formate dehydrogenase (FDH) is an abundant enzyme that plays an important role in energy supply of methylotrophic microorganisms and in response to stress in plants. FDH belongs to the superfamily of D-specific 2-hydroxy acid dehydrogenases. FDH is widely accepted as a model enzyme to study the mechanism of hydride ion transfer in the active center of dehydrogenases because the reaction catalyzed by the enzyme is devoid of proton transfer steps and implies a substrate with relatively simple structure. FDH is also widely used in enzymatic syntheses of optically active compounds as a versatile biocatalyst for NAD(P)H regeneration consumed in the main reaction. This review covers the late developments in cloning genes of FDH from various sources, studies of its catalytic mechanism and physiological role, and its application for new chiral syntheses.

Pepper Mitochondrial FORMATE DEHYDROGENASE1 Regulates Cell Death and Defense Responses against Bacterial Pathogens

“…Previous microarray analysis showed that Arabidopsis FDH was strongly induced by SA (Schenk et al, 2000). SA treatment also caused significantly higher NADH levels, which function as an electron donor in key metabolic pathways that become NAD + (Ishikawa et al, 2010 Previous studies showed that several FDH sequences were well conserved in plants (Olson et al, 2000;Tishkov and Popov, 2004;David et al, 2010). Pepper FDH1 shares a high similarity with other plant FDHs and contains a putative mitochondrial targeting sequence.…”

“…FDH1 encodes a 1,143-nucleotide open reading frame; FDH1 protein contains 381 amino acids with a predicted molecular mass of 42 kD and isoelectric point of 6.84. Sequence analysis by SignalP server 3.0 (http://www.cbs.dtu.dk/services/SignalP/) indicates that pepper FDH1 contains a signal peptide of 15 amino acids (MAMRRVASTAARAFA) and a putative cleavage site between Ala-28 and Ser-29, which was observed in the orthologs of potato, barley, and rice (Oryza sativa; Tishkov and Popov, 2004;Supplemental Fig. S2).…”

Formate as an Auxiliary Substrate for Glucose-Limited Cultivation of Penicillium chrysogenum : Impact on Penicillin G Production and Biomass Yield

“…Firstly, the high rates of NAD ϩ -dependent formate oxidation may have led to an increased intracellular NADH concentration, which, in turn, may have affected NAD ϩ -dependent reactions delivering precursors for the synthesis of penicillin G. Indeed, it has been reported that glycolysis in microorganisms may be inhibited by the addition of formate via an effect of the FDH reaction on the NADH/ NAD ϩ ratio (6,7,19,34). Secondly, it has been found that the affinity of Saccharomyces cerevisiae FDH for formate is negatively affected by high NADH/NAD ϩ ratios, showing that FDH from S. cerevisiae obeys sequential bi-bi two-substrate kinetics (12,30,37). If the same holds for P. chrysogenum, this kinetic mechanism may have contributed to the rapid increase of the residual formate concentration at high formate-to-glucose ratios, which may have caused further toxic effects.…”

Genome Sequence ofAzotobacter vinelandii, an Obligate Aerobe Specialized To Support Diverse Anaerobic Metabolic Processes

“…While best BLAST (1) hits of fdhD are against Pseudomonas spp., including P. stutzeri A1501 (E value, 10 Ϫ84 ), the catalytic subunit of FDH encoded by fdhGHI shows significant similarity to the alpha, beta, and gamma subunits of the well-studied nitrate-inducible Fdh-N enzyme from enterobacteria, including E. coli (85). Similarity E values against E. coli O157 were as follows: for fdhG, 0.0; for fdhH, 10 Ϫ129 ; and for fdhI, 10 Ϫ48 .…”