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Affordable sialoglycans and associated reagents for expanded chemoenzymatic production

用于扩大化学酶生产的经济实惠的唾液酸聚糖和相关试剂

基本信息

批准号：
10693333
负责人：
Lim Andrew Lee
金额：
$ 65.34万
依托单位：
INTEGRATED MICRO-CHROMATOGRAPHY SYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10693333
关键词：
Acids Amines Animals Bacterial Infections Basic Science Binding Proteins Biological Biotinylation Carbon Cell surface Chemicals Collaborations Communities Complex Cytolysis Diagnostic Disaccharides Disease Enzymes Equilibrium Event Family Family member Fermentation Future Glycolipids Glycoproteins Goals Homeostasis Homologous Gene Human Human Biology Human Milk Human Pathology Human body Hydrophobicity In Situ Industry Infrastructure Malignant Neoplasms Mammals Methods Molecular Probes Monitor Monosaccharides N-Acetylneuraminic Acid Neoplasm Metastasis Oligosaccharides Pathogenesis Pathologic Processes Physiological Processes Play Polysaccharides Price Process Production Productivity Property Protein Engineering Protocols documentation Reaction Reaction Time Reagent Research Role Sales Sialic Acids System Techniques Testing Therapeutic Vertebral column Virus Diseases candidate identification commercialization commercialization readiness cost glycosylation glycosyltransferase human disease immunoregulation improved innovation large scale production mannosamine manufacture mutant research and development sugar sugar nucleotide therapeutic development

项目摘要

Project Summary Sialoglycans are sialic acid-containing oligosaccharides that play important biological roles in human biology and pathology and are indispensable molecular probes for research related to bacterial and viral infection, cancer metastasis, immune regulation, etc. The multifaceted functions of sialoglycans in human milk are also being explored. Nevertheless, sialoglycan-related research and development of therapeutics and diagnostics have been hampered by the limited access to these structurally complex compounds as well as the high cost and special expertise needed for synthesizing and purifying these reagents. Among various synthetic strategies for producing sialoglycans, glycosyltransferase-based chemoenzymatic methods are attractive strategies. An efficient method for synthesizing structurally defined sialoglycans is one- pot multienzyme (OPME) chemoenzymatic strategy developed by Dr. Hai Yu and Dr. Xi Chen at UC Davis. Each OPME glycosylation reaction contains a glycosyltransferase and enzymes involved in generating the corresponding sugar nucleotide donor in situ from a simple monosaccharide. The OPME reactions allow the synthesis of target glycans containing the desired glycosidic linkage with high regio- and stereo-specificity. At the current stage, large-scale synthesis by the OPME systems is still limited by the scales and the yields of the enzymes produced. In addition, OPME reaction conditions can be improved to decrease the amounts of enzymes used for the synthesis. Product purification processes can also be streamlined using innovative strategies. To advance sialic acid-related research and therapeutic development, the goal of this proposed project is to develop reagents, enzymes, and methods that are ready for commercialization to allow low-cost access to sialoglycans of high demands and their underlying asialoglycans by the broad scientific community (both academic and industry) and to enable highly efficient production of diverse biologically important special sialoglycan targets by even nonspecialists. This will be achieved by the collaboration of the UC Davis team with IMCS which has expertise in high-yield enzyme production by fermentation, unique lysis technique, commercial infrastructure to manufacture, and product sale at affordable prices to the community.

项目总结