Reductase-epimerase-dehydrogenase

DFR belongs to the single-domain-reductase/epimerase/dehydrogenase (RED) protein family, which has also been termed the short chain dehydrogenase/reductase (SDR) superfamily. This contains other flavonoid biosynthetic enzymes, in particular the anthocyanidin reductase (ANR), leucoanthocyanidin reductase (EAR), isoflavone reductase (IFR), and vestitone reductase (VR), as well as mammalian, bacterial, and other plant enzymes. ... 

Labesse, G. et al., Structural comparisons lead to the definition of a new superfamily of NAD(P)(H)-accepting oxidoreductases the single-domain reductases/epimerases/dehydrogenases (the RED family). Biochem. J., 304, 95, 1994. 

Figure I. The fungal and bacterial pathways for D-xylose and L-arabinose catabolism. All pathways have in common that D-xylulose 5-phosphate is produced. The enzymes in the bacterial pathways are xylose isomerase and xylulokinase for the D-xylose pathway and L-arabinose isomerase, ribulokinase and L-ribulosephosphate 4-epimerase for the L-arabinose pathway. The fungal D-xylose pathway has the enzymes aldose reductase, xylitol dehydrogenase and xylulokinase. The enzymes in the L-arabinose pathways ofmold and yeast are aldose reductase, L-arabinitol 4-dehydrogenase, L-xylulose reductase, xylitol dehydrogenase and xylulokinase. The differences between the mold and yeast pathway are in the cofactor requirements.

Dehydrogenases, reductases and a number of other enzymes, such as UDP-glucose epimerase, utilize NAD or NADP as an enzymatic cofactor and catalyze the oxidation/reduction of various substrates, facilitating the usually reversible stereospecific hydride transfer from the C4 position of the 1,4 dihydronicotinamide ring of NAD(P)H to substrate. The reaction catalyzed by lactate dehydrogenase and a schematic drawing of the putative hydride transfer reaction that takes place are shown in Fig. 15.1. 

Fig. 8. P-Oxidation of fatty acids in E. coli. Long-chain fatty acids are transported into the cell by FadL and converted to their CoA thioesters by FadD (not shown). The acyl-CoAs are substrates for the (1) acyl-CoA dehydrogenase (YafH) to form a trans-2-enoyl-CoA. The double bond is reduced by (2) rrans-2-enoyl-hydratase (crotonase) activity of FadB. The P-hydroxyacyl-CoA is then a substrate for the NADP -dependent dehydrogenase activity of FadB (3). A thiolase, FadA (4), releases acetyl-CoA from the P-ketoacyl-CoA to form an acyl-CoA for subsequent cycles. (5) Polyunsaturated fatty acyl-CoAs are reduced by the 2,4-dienoyl-CoA reductase (FadH). (6) FadB also catalyzes the isomerization of c/s-unsaturated fatty acids to trans. (7) The epimerase activity of FadB converts O-P-hydroxy thioesters to their L-enantiomers via the /rans-2-enoyl-CoA.

Fig. 5. A simplified metabolic scheme of ethanol formation from glucose and xylose. Enzyme abbreviations GPDH Glucose 6-phosphate 1-dehydrogenase, PGDH Phosphogluconate dehydrogenase, PGI Glucose 6-phosphate-isomerase, RKI Ribose 5-phosphate isomerase, RPE Ribulose phosphate 3-epimerase, TAL Transaldolase, TKL Transketolase, XDH Xylitol dehydrogenase, XK-. Xylulokinase, XR Xylose reductase...

Fig. 2 Metabolic routes for mcl-PHA biosynthesis. Pseudomonas putida GPol synthesizes PHA through P-oxidation and P. putida KT2440 synthesizes PHA through fatty add de novo synthesis. Special PHA consisting of 4-hydroxyalkanoate, 5- hydroxyalkanoate, or 6-hydroxyalkanoate can be produced by various bacteria when suitable precursors are supplied. 1 acyl-CoA synthetase, 2 acyl-CoA dehydrogenase, 3 enoyl-CoA hydratase, 4 NAD-dependent (5)-3-hydroxyacyl-CoA dehydrogenase, 5 3-ketoacyl-CoA thiolase, 6 (ItFspecific enoyl-CoA hydratase, 7 NADPH-dependent 3-ketoacyl-CoA reducatase, 8 3-hydroxyacyl-CoA epimerase, 9 mcl-PHA polymerase, 10 acetyl-CoA carboxylase, 11 malonyl-CoA-acyl carrier protein (ACP) tiansacylase, 12 3-keto-ACP synthase, 13 3-keto-ACP reductase, 14 3-hydroxyacyl-ACP dehydratase, 15 enoyl-ACP reductase, 16 acyl-ACP thiolase, 17 (l )-3-hydroxyacyl-ACP-CoA transacylase, 18 mcl-PHA polymerase...

Figure 6.2 Sequential cascade reaction for the synthesis of dTDP-deoxy sugars, (a) dTMP-kinase, (b) pyruvate kinase, (c) sucrose synthase (SuSy), (d) dTDP-GIc 4,5-dehydratase (RmlB), (e) 3,5-epimerase (RmIC or DnmU), (f) 4-keto reductase (RmID), and (g) formate dehydrogenase [82].

Figure 14 Production of 3-hydroxypropionic add as a nrtetabolic intermediate and an end product via 3-hydroxypropionate pathway in ChlCH ofiexus aurantiacus. Enzymes accACD, acetyl-CoA carboxylase mcr, malonyl-CoA reductase pcs, propionyl-CoA synthase pcc, propionyl-CoA carboxylase mcee, methylmalonyl-CoA epimerase mut, methylmalonyl-CoA mutase smtAB, sucdnyl-CoA (S)-malate-CoA transferase sdh, succinate dehydrogenase fh, fumarate hydratase mcl, (S)-malyl-CoA/-methylmalyl-CoA/(S)-citramalyl-CoA (MMC) lyase mch, methylmalyl-CoA dehydratase met, mesaconyl-CoA-Cl-C4 CoA transferase and meh, mesaconyl-C4-CoA hydratase [10] (Reference Metacyc).

Different pathways are available in nature for metabolism of arabinose and xylose which are converted to xylulose 5-phosphate (intermediate com-poimd) to enter the pentose phosphate pathway as shown in Figure 10.5. In yeasts, xylose is first reduced by xylose reductase to xylitol, which in turn is oxidized to xylulose by xylitol dehydrogenase. In bacteria and some anaerobic fungi, xylose isomerase is responsible for direct conversion of xylose to xylulose. Xylulose is finally phosphorylated to xylulose-5-phos-phate by xylulokinase. In fungi, L-arabinose is reduced to L-arabitol (by arabinose reductase), L-xylulose (by arabitol dehydrogenase), xylitol (by L-xylulose reductase). Xylitol is finally converted to xylulose (by xylitol dehydrogenase), whose activity is also part of xylose utilization pathways. In bacteria, L-arabinose is converted to L-ribulose (by L-arabinose isomerase), L-ribulose-5-P (by L-ribulokinase) and finally D-xylulose-5-P (by L-ribulose-5-P 4-epimerase) (Bettiga et al., 2008). 

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