Carbohydrate synthesis enzymatic methods

In summary, for aU of the above-mentioned applications, the synthesis of carbohydrates and derivatives thereof is necessary to foster the field of glyco-engineering. Many procedures have been established to produce synthetic (neo)glycoconjugates by chemical or enzymatic methods and these are summarized in excellent reviews [12, 27, 28]. 

The most widely adopted methods for carbohydrate synthesis utilize either enzymatic or chemical approaches. Enzymatic carbohydrate synthesis is a vibrant area of research that has been reviewed thoroughly and will... 

Despite their widespread occurrence in nature, and despite some members of the class being available at scale, carbohydrates and hydroxy acids have not found widespread application as synthons in large-scale line chemical synthesis with the exception of food ingredients. This is presumably a result of the problems associated with the differentiation of very similar functional groups, although enzymatic methods are known, and the low atom efficiency when incorporated into a synthesis. 

Remarkable advances have been made in the synthesis of N- and O-glycosylated amino acids that, in addition to the 5-fattyacyl-cysteine, are the most sensitive derivatives to the conditions of peptide synthesis. The fine tuning of both carbohydrate and peptide chemistry as well as the use of enzymatic methods are required for the synthesis of glycopeptides. " Similarly soft chemistry has to be applied in the case of S-acylated peptides, whereas fat-tyacylation at amino groups raises no additional difficulties.The state of the art in the field of glyco- and lipopeptide synthesis is discussed in details in Vol. E22b, Sections 6.3 and 6.4, respectively. 

As is evident from the work that is reviewed here, the application of biocatalysts in preparative carbohydrate synthesis has continued to expand and diversify in recent years. Of particular note is the reengineering of biocatalyst properties (e.g., substrate specificity, stability) by the process of directed evolution. Significant progress in the study of the enzymatic biosynthesis of complex carbohydrate has been made with the development in protein purification, molecular genetics, and new methods of enzymological analysis. Bioinformatics provides a large number of putative candidates for carbohydrate-active enzymes. The combined... 

Some years ago, we started a project aimed at the development of simple and efficient enzymatic methods for the synthesis of biologically-active carbohydrates on a preparative scale. The use of enzymes as catalysts for the synthesis of carbohydrates has many potential advantages, such as enabling selective, stereo specific syntheses with a minimum of reaction steps under mild conditions and in aqueous solutions in which carbohydrates are highly soluble. Moreover, many enzymes now can be produced in quantity by fermentation and can be immobilized and reused. 

Likewise, starting a synthesis with an enantiomerically pure compound which has been selected from the large stock of enantiopure natural compounds [77] such as carbohydrates, amino acids, terpenes or steroids - the so-called chiral pool -has its limitations. According to a survey from 1984 [78] only about 10-20% of compounds are available from the chiral pool at an affordable price in the range of US 100-250 per kg. Considering the above-mentioned problems with the alternative ways of obtaining enantiomerically pure compounds, it is obvious that enzymatic methods represent a valuable addition to the existing toolbox available for the asymmetric synthesis of fine chemicals [79]. 

Part 1 of Carbohydrates in Chemistry and Biology is designed to be a valuable collection of chemical and enzymatic methods for the synthesis of oligosaccharides. It also covers state-of-the-art knowledge of the interactions of carbohydrates with their natural receptors. Each of the chapters is written by a leading expert in the field and covers an impressive body of references. 

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