Disaccharides biosynthesis

Figure 48-9. Structure of heparin. The polymer section illustrates structural features typical of heparin however, the sequence of variously substituted repeating disaccharide units has been arbitrarily selected. In addition, non-O-sulfated or 3-0-sulfated glucosamine residues may also occur. (Modified, redrawn, and reproduced, with permission, from Lindahl U et al Structure and biosynthesis of heparin-like polysaccharides. Fed Proc 1977 36 19.)...

The biosynthetic pathway described above indicates the possible involvement of multifunctional enzyme con5>lexes in the biosynthesis of the peptide part of bleomycin. The peptide peurt of bleomycin has no cytotoxicity. Probably, in the final step of the biosynthesis, the disaccharide peirt is transferred to the B-hydroxyl group of the B-l droxylhistidyl moiety and the bleomycin thus synthesized is rapidly released extracellularly. 

An understanding of the structures of the molecules of heparin and heparan sulfate has come, in part, from studies with degradative enzymes, but also with biosynthetic enzymes. Both polysaccharides are based on the disaccharide unit which, in the initial stage of biosynthesis, consists of... 

The structures of polyprenyl diphosphate-linked intermediates of Salmonella O-specific-polysaccharide biosynthesis were confirmed by chemical synthesis of their analogs derived from the plant polyprenols ficaprenol and moraprenol (structurally related to bacterial polyprenol57) with the following study of their behavior as substrates of enzymic reactions. Synthetic polyprenyl a-D-galactopyranosyl diphosphate291,292 was found to serve as an effective acceptor for the transfer of L-rhamnosyl groups.293"295 Two synthetic, isomeric disaccharide derivatives,292 13 and296 14, were tested as acceptors for enzymic D-mannosyl transfer from GDP-Man, but only the former was found to be an efficient substrate.294... 

It was shown that, in the maturing seeds, while the synthesis of reserve hemicellulose progresses in the endosperm, a large amount of a trehalose is formed, in addition to sucrose and umbelliferose.92 This trehalose disappears rapidly during the progress of the ripening process, and umbelliferose accumulates continuously. It was predicted that the trehalose may be present in most umbellifers however, the relationship of this disaccharide to the biosynthesis of umbelliferose, and the mechanism involved therein, are not known. 

E. Fernandez, U. Weissbach, C. Sanchez Reillo, A. F. Brana, C. Mendez, J. Rohr, and J. A. Salas, Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin, J. Bacteriol., 180 (1998) 4929 1937. 

Another structural consideration relevant to biosynthesis is the fact that, within a chain, each D-glucosyl residue is rotated approximately 180° with respect to its neighbor, as depicted in 1. Thus, cellobiose may actually be considered to be the true repeating-unit within the chain, and it is necessary to consider whether some activated form of the disaccharide (rather than of D-glucose) might be the donor for chain elongation this point will be considered again in Section V,2. 

From these results, it may be concluded that the pseudo-disaccharide 44 is the first intermediate in the assembling of the three components of dihydrostreptomycin. The fact that no transfer-product was observed with streptidine is in agreement with the conclusions from a number of studies in which the importance of phosphorylated intermediates in the biosynthesis of streptomycin was established.36,64,65... 

Scheme 20a, b. Disaccharide transfers are thought to be involved in the biosynthesis of acarbose (16, transfer of maltose) and landomycin A (12, transfer of diolivoside units)... 

Figure 5 Biosynthesis and structure of glycosaminoglycans. Synthesis u GlcAT-l. The repeating disaccharides of heparin/HS, CS, and DS are shown.

KSII biosynthesis is initiated by the formation of mucin-type core 2 disaccharide (103). KSn is usually capped with siahc acid at either C3 or C6 of terminal GlcNAc. Sulfated GlcNAc in KSn is often modified with al-3-hnked fucose, although uot within four sugars of the terminus (104). 

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