Activated hexosamines from chitin for production of important oligosaccharides

描述（由申请人提供）：UDP-GlcNAc和UDP-GalNAc构成糖蛋白和糖脂中聚糖的核心结构。含有n -乙酰己糖胺的寡糖参与多种生物过程，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。含有这些糖的核心结构的寡糖是研究细胞信号传导过程和代谢调节所必需的；这些低聚糖已被广泛研究作为抗菌剂和潜在的抗癌疫苗。这些应用开发的限制因素是高生产成本和UDP-GlcNAc和UDP-GalNAc构建块的低可用性。成本因素包括缺乏有效的酶系统来制造这些活性糖，大量的纯化步骤，以及三磷酸核苷的成本。在这里，我们建议开发一种大规模生产母乳低聚糖和其他低聚糖的两种主要成分的技术，UDP-GlcNAc和UDP-GalNAc，从自然界中最丰富的生物聚合物之一，几丁质。在第一阶段，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专有的酶将其转化为UDP- glcnac、UDP- GalNAc、globotetraose和lactto - n -triose 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 -乙酰己糖的反应条件，扩大我们的糖硅转移酶文库，以生产重要的低聚糖：globotetraose，核心牛奶低聚糖乳酸-n -四糖，乳酸-n -neo-四糖及其衍生物。最后，在第三阶段商业化中，我们将销售UDP- GlcNAc/GalNAc和低聚糖。

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.