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Activated hexosamines from chitin for production of important oligosaccharides

甲壳素中的活化己糖胺用于生产重要的寡糖

基本信息

批准号：
8714672
负责人：
Leila Aminova
金额：
$ 16.82万
依托单位：
ZUCHEM, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8714672
关键词：
Acetylgalactosamine Acetylglucosamine Anabolism Anti-Infective Agents Antibiotics Antigens Bacteria Biological Process Biopolymers Blood Blood typing procedure Cell Signaling Process Chitin Chitinase Cloning Coupling Development Economics Enzymes Epitopes Escherichia coli Food Supplements Glycolipids Glycoproteins Goals Health Hexosamines Housing Human Human Milk Infection Lactose Libraries Lipids Marketing Metabolic Methods Milk Modification N acetylhexosamine N-acetylglucopyranosylamine Nature Neoplasm Metastasis Oligosaccharides Phase Phosphorylase Kinase Phosphotransferases Polymers Polysaccharides Production Proteins Reaction Recombinants Regulation Research Structure System Techniques Technology Testing Therapeutic Therapeutic Uses Toxin Trioses Uridine Uridine Diphosphate Galactose Vaccines anti-cancer therapeutic antimicrobial drug blood group cancer cell commercialization cost cost effective epimerase expression vector globotetraose globotriose glycosyltransferase improved inorganic phosphate interest lacto-N-neotetraose large scale production microbial nucleoside triphosphate nutrition overexpression prospective public health relevance scale up sugar sugar nucleotide tool

项目摘要

DESCRIPTION (provided by applicant): UDP-GlcNAc and UDP-GalNAc comprise the core structures of glycans in glycoproteins and glycolipids. Oligosaccharides containing N-acetyl-hexosamines involved in various biological process, including microbial infection, toxin entry, cancer cell metastasis. They are the key building blocks for human milk oligosaccharides, blood antigens, and other important oligosaccharides. Oligosaccharides with core structures containing these sugars are needed for investigating cell signaling processes and metabolic regulation; these oligosaccharides have intensively been investigated as antimicrobial agents and prospective anticancer vaccines. The limiting factor in the development of these applications is the high production cost and low availability of the UDP-GlcNAc and UDP-GalNAc building blocks. Cost factors include a lack of effective enzymatic systems for making these activated sugars, extensive purification steps, and the cost of nucleoside triphosphates. Here we propose to develop a technology for the large-scale production of two main components of human milk oligosaccharides and other oligosaccharides, UDP-GlcNAc and UDP-GalNAc, from one of most abundant biopolymers in nature, chitin. In Phase I we will select set of enzyme that will enable effective conversion of chitin to GlcNAc-1-phosphate, using zuChem proprietary enzymes will transform to UDP-GlcNAc, UDP- GalNAc, globotetraose and lacto-N-triose II and analyze economic efficiency of this conversion. In Phase II we will optimize reaction condition for large scale production of activated N-acetylhexosamine, expand our library of glycosiltransferases for production of important oligosaccharides: globotetraose, core milk oligosaccharides Lacto-N-tetraose, Lacto-N-neo-tetraose and they derivatives. Finally in Phase III commercialization we will sell UDP- GlcNAc/GalNAc and oligosaccharides.

描述（由申请人提供）：UDP-GlcNAc和UDP-GalNAc包含糖蛋白和糖脂中聚糖的核心结构。含有N-乙酰己糖胺的寡聚体参与多种生物学过程，包括微生物感染、毒素进入、癌细胞转移。它们是人乳低聚糖、血液抗原和其他重要低聚糖的关键组成部分。研究细胞信号传导过程和代谢调节需要含有这些糖的核心结构的寡糖;这些寡糖已被广泛研究作为抗菌剂和前瞻性抗癌疫苗。开发这些应用的限制因素是UDP-GlcNAc和UDP-GalNAc结构单元的高生产成本和低可用性。成本因素包括缺乏用于制备这些活化糖的有效酶系统、广泛的纯化步骤和核苷三磷酸的成本。在这里，我们建议开发一种技术，用于大规模生产人乳低聚糖和其他低聚糖的两个主要成分，UDP-GlcNAc和UDP-GalNAc，从自然界中最丰富的生物聚合物之一，甲壳素。在阶段I中，我们将选择一组能够将几丁质有效转化为GlcNAc-1-磷酸的酶，使用zuChem专有酶将其转化为UDP-GlcNAc、UDP-GalNAc、球四糖和乳糖-N-丙糖II，并分析这种转化的经济效率。在第二阶段，我们将优化大规模生产活化N-乙酰己糖胺的反应条件，扩大我们的糖苷转移酶库，用于生产重要的寡糖：球四糖，核心乳寡糖乳糖-N-四糖，乳糖-N-新-四糖及其衍生物。最后，在第三阶段商业化中，我们将出售UDP-GlcNAc/GalNAc和寡糖。