DTDP-sugar

Scheme 5.5 In situ regeneration of dTDP-sugars. (A) SuSy module, (B) deoxy sugar module and (C) glycosyltransferase module [33]. 

On the basis of these results, the authors16 proposed the reaction sequence shown in Scheme 4 for the biosynthesis of CDP-L-vinelose from CDP-D-glucose. As with L-mycarose, the 6-deoxyhexos-4-ulose derivative (11) is the substrate for the methylation step leading to the CDP-6-deoxy-3-C-methylhexos-4-ulose (12). The corresponding dTDP-sugar might, therefore, be one of the unidentified reaction-products in the biosynthesis of dTDP-L-mycarose. 

SCHEME 7.—Reactions Proposed for the Biosynthesis of the Oxoethyl-branched dTDP-sugar 19 from dTDP-D-glucose in a Cell-free System from S. aureofaciens. 

The transfer of dTDP sugars into the lactone moiety to form glycoside linkage is mediated by individual glycosyltransferase as follows EryBV [4] and lyiCV... 

Glycosylation is catalyzed by glycosyl transferases, which use dTDP-sugar substrates. Separate transferases usutdly add each component. In terms of generating novel glycosides, the transferases are obviously key enzymes. 

The broad substrate specificity is also illustrated in cases where new dTDP sugars have been produced in anthracycline production strains by genetic engineering. The important doxorubicin analog epirubicin, previously produced by semisynthetic means, could be produced by artificially modifying the dTDP-amino sugar production pathway in S. peucetius [13] (see below). 

DSC the acronym of Differential scanning calorimetry. See Membrane lipids. d1T>P see Thymidine phosphates. dTDP-sugars sugars or sugar derivatives activated by bonding to deoxythymidine diphosphate sugars dThd acronym of deoxythymidine. see Thymidine. dTMP see Thymidine phosphates. dTTP see Thymidine phosphates. 

The simultaneous replacement of uridine by deoxythymidine and galactose by a number of deoxy sugars to give non-natural donor substrates has also been reported [50], Partially protected a-sugar-1-phosphates were coupled to morpholidate-activated deoxythymidine-5-phosphate and subsequently deprotected in the presence of lithium hydroxide to give the corresponding dTDP sugars (see Table 1). 

Rupprath, C., Kopp, M., Hirtz, D. et al. (2007) An enzyme module system for in situ regeneration of deoxythymidine 5 -diphosphate (dTDP)-activated deoxy sugars. Advanced Synthesis Catalysis, 349, 1489-1496. 

In order to provide dTDP-deoxy sugars by combinatorial biocatalysis we have utiHzed the enzymes for the dTDP- 3-L-rhamnose pathway. The successful combination of pathway enzymes with optimized enzyme productivities (amount of product per unit of enzyme) needs a concise kinetic and inhibition analysis. Scheme 5.1 depicts the biosynthetic pathway of dTDP- 3-L-rhamnose with important km and Ki constants. The enzymes RmlA and RmlB are highly controlled by the intermediate, dTDP-4-keto-6-deoxy-a-D-glucose 3, the product 5 or by... 

With 2-deoxy-D-glucose-6-phosphate 6 as starting substrate and an additional enzymatic step the synthesis of dTDP-2,6 dideoxy-4-ketoglucose 7, an important intermediate of dTDP-deoxy sugars, and dTDP-P-L-olivose 8 was realized (Scheme 5.2) [68]. 

The sugar nucleotides (an uninformative name that has been used for glycosyl nucleotides, or more strictly, glycosyl esters of nucleoside di- or mono-phosphates) were discussed in this Series12 in 1973. Since then, accumulation of new data about these derivatives has continued, and now, about 35 representatives of this class are known to participate in the biosynthesis of polysaccharide chains of bacterial polymers (for a survey, see Ref. 13). These include glycosyl esters of uridine 5 -diphosphate (UDP), thymidine 5 -diphosphate (dTDP), guanosine 5 -diphosphate (GDP), cytidine 5 -diphosphate (CDP), cytidine 5 -monophosphate (CMP), and adenosine 5 -diphosphate (ADP). 

The currently known structures of bacterial polysaccharides may be separated into several, biosynthetic types according to the nature of the activated forms of the monosaccharide residues in the main chain (for example, the UGT type means that UDP-, GDP-, and dTDP-activated sugars are present in the main chain). Table VIII shows the total number... 

Recently, some knowledge was acquired concerning nature s approach to the synthesis of dideoxy sugars. 6-Deoxygenation of glucose seems to follow a redox pathway via the nucleotide glucoside dTDP-glucose with oxidoreductase which leads to a 6-deoxy-4-uloside [1],... 

As shown in the biosynthesis of granaticin, a hydride shift occurs intramolecularly. This process is mediated by an enzyme-bond pyridine nucleotide. A concerted abstraction of H-4 as a hydride in la and a C-5 deprotonation in 2a leads to the 4,5-enol ether 3a. The reduced form of the pyridine nucleotide transfers the hydride to C-6, simultaneously releasing a hydroxide to give 4a. Final tautomerization yields the dTDP-4-keto-6-deoxy-sugar in v-xylo configuration 4a. In other enzymes of the oxidoreductase type, the active site may show a different configuration. Thus, the intermediate 3a can be protonated from above at C-5 to yield the l-arabino isomer of 4a [2]. The stereochemistry of this mechanism was demonstrated by double labelling (cf. l-4b series), and as a net result proved a suprafacial 4—>6 hydride shift. 

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. 

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