Glycosynthases: a Novel Efficient Synthetic Tool for Oligosaccharides
- VernacularTitle:糖苷合成酶——一类新型的寡糖高效合成工具
- Author:
Lili LU
;
Min XIAO
;
Han ZHAO
;
Peng WANG
;
Xinmin QIAN
- Publication Type:Journal Article
- Keywords:
oligosaccharides synthesis, glycosidases, glycosynthases, screening in high-throughput assay, improvement of characteristics
- From:
Progress in Biochemistry and Biophysics
2006;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Oligosaccharides are one of the essential physiological constituents of glycoproteins and glycolipids on mammalian cell surfaces and microbial metabolites. They have considerable potential as therapeutics but are only now slowly assuming this important role. One of the reasons for their slow development has been the considerable difficulty in synthesizing oligosaccharides on the scale necessary for their clinical evaluation. Classical chemical and enzymatic methods both have limitations in synthesizing large-scale oligosaccharides. In recent years, the rapid progress on molecular biotechnology has promoted the development of retaining glycosidases in oligosaccharides synthesis, which led to the production of a novel class of enzymatic activities termed the glycosynthases. These new enzymes are retaining glycosidase mutants in which the catalytic nucleophile has been converted to a non-nucleophilic residue,synthesizing oligosaccharides in high yields ( the highest yields reach 99%) without any hydrolysis. Furthermore thioglycoligases and thioglycosynthases have been developed subsequently in the past three years. Glycosynthases can be screened in high-throughput assay by the two-plasmid system and the yeast three-hybid system respectively. Their activity can be significantly enhanced by substituting alternative residues for nucleophile, additional random mutations and optimizing reaction conditions. Their regioselectivity can be modified through changes in receptors.
