Sugar dehydratase

In enolase, the substrate, 2-phosphoglycerate (2-PGA) is coordinated to two Mg ions, one of which is liganded to the three conserved carboxylate residues (Asp 246, Glu 295, and Asp 320). Currently, more than 600 enolase sequences have been identified in the databases, and aU are thought to be isofunctional, catalyzing the conversion of 2-PGA to phosphoenolpyruvate. In the MLE subclass of the superfamily, at least three reactions are known to be catalysed — in addition to the lactonisation of muconate, succinylbenzoate synthase, and L-Ala-D/L-Glu epimerase reactions are observed within the 300 members. The MR subclass catalyses at least five reactions, mandelate racemisation and 4 sugar dehydratases. As in the MLE subclass, of the 400 members identified, only 50% of these are functionally assigned. 

Some amino sugar dehydratases use pyridoxamine phosphate 6 as a cofactor. The enzyme CDP-4-keto-6-deoxy-D-glucose reductase (EC 1.17.1.1) is one such enzyme, catalyzing the process shown in Scheme 10. 

Many DOHs, such as L-daunosamine, L-epivancosamine or L-ristosamine, contain an amino group at C3, which is introduced by an aminotransferase. The substrate for this reaction is the 3-keto sugar intermediate that arises as a consequence of the action of a 2,3-dehydratase. This transaminahon reaction has been biochemically characterized in the biosynthesis of L-epivancosamine [10]. Using a coupled reaction with EvaB (2,3-dehydratase) and EvaC (aminotransferase), with pyridoxal-5-phosphate (PEP) as a coenzyme and L-glutamate as a cosubstrate, they were able to show conversion of TDP-4-keto-2,6-dideoxyglucose into thymidine-5 -diphospho-3-amino-2,3,6-trideoxy-D-threo-hexopyranos-4-ulose. 

The key intermediates in the biosynthesis of 6-deoxy sugars are the nucleoside 6-deoxyhexosyl-4-ulose diphosphates (7), formed through enzymic reactions catalyzed by NDP-sugar 4,6-dehydratases (EC 4.2.1.45-47) from primary glycosyl nucleotides. These reactions were observed... 

A. Naundorf and W. KlaHke, Substrate specificity of native dTDP-D-glucose-4,6-dehydratase chemo-enzymatic syntheses of artificial and naturally occurring deoxy sugar, Carbohydr. Res., 285 (1996) 141-150. 

Most NAD(P)-dependent oxidoreductases, dehydratases, and epimerases are members of either the aldo-keto reductase (AKR) superfamily or the SDR superfamily. Proteins in the AKR family share a common (a//3)g-barrel fold and are involved in the metabolism of many important compounds including aldehydes, sugars, and... 

Fig. 4 Reaction mechanism of dTDP-glucose 4,6-dehydratase as proposed by Allard et al. [125], The first half of the reaction involves abstraction of a proton from the 4 hydroxyl group, and hydride transfer from C-4 to NAD. In the next step, a proton is removed from the C-5 atom of the sugar, and the C-6 hydroxyl group is protonated and eliminated as water. This yields the 4-keto-5,6-ene intermediate. The product is obtained after hydride transfer from NADH to carbon atom C-6 and protonation of carbon atom C-5...

L-lsoieucine, lie L-a-amino-P-methylvaleric acid, CH3-CH2-CH(CH3)-CH(NH2)-C00H, an aliphatic, neutral amino acid found in proteins. He is found in relatively large amounts in hemoglobin, edestin, casein and serum proteins, and in sugar beet molasses, from which it was first isolated in 1904 by F. Ehrlich. It is an essential dietary amino acid, and is both glu-coplastic (degradation via propionic acid) and keto-plastic (formation of acetate) (see Leucine), The biosynthesis of He starts with oxobutyrate and pyruvate. Oxobutyrate is synthesized by deamination of L-threonine by threonine dehydratase (threonine de-... 

CoA units. In Scheme 11.38, the abbreviations are KS, ketosynthase AT, acyl transferase ACP, acyl carrier protein KR, ketoreductase ER, enoyl reductase DH, dehydratase and TE, thioesterase (to remove the completed chain prior to or concomitant with) cyclization. Finally, as also seen in Scheme 11.38, the formation of erythromycin A requires some small oxidative modifications (and attachment of two sugars at the anomeric carbon) for completion. 

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].

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