6-Deoxyhexoses biosynthesis

I Modifying the Glycosflation Pattern in Aainomycetes by Combinatorial Biosynthesis 6-deoxyhexoses... 

For most of the sugar components, little or nothing is known about their biosynthesis. Nucleoside hexosyl-4-ulose diphosphates are, however, almost certainly key intermediates in the biosynthesis of several of these sugars, as discussed in Ref 7. The biosynthesis of the 6-deoxyheptoses is probably analogous to that of the 6-deoxyhexoses, and proceeds by way of nucleoside heptosyl-4-ulose diphosphates. 

Not much has been added to the biochemistry of STRs in the recent years. Therefore, we will only briefly treat the biosynthetic pathway here. Biosynthesis of the aminocyclitol (streptidine) and 6-deoxyhexose (streptose) moieties are well understood, with some remaining gaps in the enzymology. Much less is known about the residual biosynthetic phases, the formation of A-methyl-L-glucosamine, the condensation of subunits, and the late modification steps potentially coupled with export. ... 

Chapters 17 through 21 deal with carbohydrate-enzyme systems. Hehre presents some new ideas on the action of amylases. Kabat presents some new immunochemical studies on the carbohydrate moiety of certain water-soluble blood-group substances and their precursor antigens. Hassid reviews the role of sugar phosphates in the biosynthesis of complex saccharides. Pazur and co-workers present information obtained by isotopic techniques on the nature of enzyme-substrate complexes in the hydrolysis of polysaccharides. Gabriel presents a common mechanism for the production of 6-deoxyhexoses. An intermediate nucleoside-5 -(6-deoxyhexose-4-ulose pyrophosphate) is formed in each of the syntheses. 

Subsequent Reactions Catalyzing 6-Deoxyhexose Formation 3,5-Epimerase and Reductase. After the formation of the 4-keto intermediate, a step common to all deoxyhexose formations, at least two and possibly three additional enzymes are necessary for the biosynthesis of the end product. This sequence of transformations is illustrated in Figure 3. The first step is the conversion of the 4-keto-6-deoxy-hexose intermediate described above. The intermediates in brackets are postulated and are assumed to be bound to the enzyme. An enzyme (or enzymes), referred to below as 3,5-isomerase, catalyzes epimerizations at carbons 3 and 5, probably via the enediol form. The epimerizations are followed by a... 

Enzymes Not Directly Related to 6-Deoxyhexose Biosynthesis with Similar Reaction Mechanisms... 

Gaisser S, Martin CJ, Wilkinson B et al (2002) Engineered biosynthesis of novel spinosyns bearing altered deoxyhexose substituents. Chem Commun 21 618-619... 

Gaisser S, Martin CJ, WiUdnson B, Sheridan RM, Lill RE, Weston AJ, Ready SJ, Waldron C, Crouse GD, Leadlay PE, Staunton J (2002) Engineered Biosynthesis of Novel Spinosyns Bearing Altered Deoxyhexose Substituents. Chem Commun 618... 

An instance of pathway manipulation with potentially high commercial significance was the production of epirubidn in S.peucetius [13]. The (4S)-TDP-4-keto-6-deoxyhexose reductase gene, dnmV, was disrupted by insertional inactivation, and the gene for a homologous reductase from erythromycin (EryBIV) or avermectin (AvrE) biosynthesis, with different product stereochemistry (4R), was introduced to the production strain (Scheme 9). 

Figure 2 Basic pathway design for the biosynthesis of streptomycins and speciinomycins. Fully modified precursors are ctuidensed to the final products. P2S = pseudodisaccharidc P3S pseudotrjsaccharide 6DOH = an activated 6-deoxyhexose precursor NMLGA = NDP-activated N mcthyl L glucosamme.

Ftgun 38 General paih Yay for the biosynthesis of D- and L forn s of 6 deoxyhexose 6DOH). Hexose-l-P precursors are either D-glucosc-l-P or D-mannose l P- P phosphate NDP = dTDP, CDP.orGDP. 

Figure 10.7. Biosynthesis of 6-deoxyhexoses dTDP-L-rhamnose, GDP-D-rhamnose, and GDP-L-fucose.

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