Strategies for the Chemoenzymatic Synthesis of Deoxysugar Nucleotides:  Substrate Binding versus Catalysis

• Published in: Journal of organic chemistry Vol. 70; no. 5; pp. 1919 - 1921
• Main Authors: Ko, Kwang-Seuk, Zea, Corbin J, Pohl, Nicola L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 04.03.2005
• Subjects: Binding Sites; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Carbohydrate Conformation; Carbohydrates. Nucleosides and nucleotides; Catalysis; Chemistry; Deoxyglucose - chemical synthesis; Deoxyglucose - chemistry; Deoxyribonucleotides - chemical synthesis; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Methods. Procedures. Technologies; Nucleosides, nucleotides and oligonucleotides; Nucleotidyltransferases - chemistry; Organic chemistry; Preparations and properties; Substrate Specificity; Enzymatic synthesis; Protein engineering; Catalytic reaction; Enzyme; Transferases; Glycosyltransferases; Molecular interaction; Oside; Pyrophosphorylase; Nucleotidyltransferases; Binding capacity; Nucleotide; Organic phosphate; Catalysis; Chemical synthesis; UTP-glucose-1-phosphate uridylyltransferase
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048424p

Sugar nucleotidyltransferases, also known as sugar pyrophosphorylases, catalyze the formation of a phosphate linkage to produce sugars activated for use by Leloir pathway glycosyltransferases and are subjects of protein engineering for chemoenzymatic synthesis strategies. Herein we present evidence that differences in substrate binding affinity do not primarily account for substantial contrasts in deoxysugar nucleotide product yields with this class of enzymes. Prokaryotic and eukaryotic glucose-1-phosphate uridylyltransferases (EC 2.7.7.9) can exercise kinetic discrimination in choosing carbohydrates of comparable binding affinity for catalytic turnover. These findings have implications for the in vivo and in vitro function and use of these enzymes.