Chen X, Kowal P, Wang P G
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Curr Opin Drug Discov Devel. 2000 Nov;3(6):756-63.
The increasing recognition of the roles of carbohydrates in fundamental biological processes and their potential as new therapeutics has accentuated the requirement for access to large quantities of varying carbohydrate structures. During the past two years, tremendous advances have been made in the large-scale enzymatic synthesis of oligosaccharides using isolated enzymes or engineered whole cells. Glycosidase mutants, namely glycosynthases, have been constructed to increase both the yields and selectivity of the glycoside bond formation. The use of glycosyltransferases in oligosaccharide synthesis has been further improved by fusing a glycosyltransferase with a sugar nucleotide-synthesizing enzyme and by various routes of in situ sugar nucleotide regeneration. Moreover, several sugar nucleotides and oligosaccharides were produced economically by a combination of recombinant microorganisms harboring sugar nucleotide biosynthesis genes and a glycosyltransferase gene.
碳水化合物在基本生物学过程中的作用及其作为新疗法的潜力日益受到认可,这凸显了获取大量不同碳水化合物结构的需求。在过去两年中,使用分离的酶或工程化全细胞进行寡糖的大规模酶促合成取得了巨大进展。糖苷酶突变体,即糖基合成酶,已被构建以提高糖苷键形成的产率和选择性。通过将糖基转移酶与糖核苷酸合成酶融合以及通过原位糖核苷酸再生的各种途径,糖基转移酶在寡糖合成中的应用得到了进一步改进。此外,通过将携带糖核苷酸生物合成基因和糖基转移酶基因的重组微生物组合,经济地生产了几种糖核苷酸和寡糖。