Dissection of the Leishmania mannogen biosynthetic pathway: beta 1-2 mannan in pathogens and beyond

利什曼原虫甘露原生物合成途径的剖析：病原体及其他物质中的 β 1-2 甘露聚糖

• 批准号: BB/T004819/1
• 负责人: Gideon Davies
• 金额: $ 58.9万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT004819%2F1
• 关键词: Dissection; Leishmania; mannogen; biosynthetic; pathway

Most living organisms store energy reserves in the form of glucose-based polysaccharides; glycogen in humans, and starch in plants, for example. But some organisms use more unusual forms of carbohydrate storage. As part of an international team, we have just discovered the Leishmanial parasite - the causative agent of the sandfly-transmitted Leishmaniases, for example, stores energy in the form of an unusual polysaccharide termed 'mannogen'. Formation of this energy store is essential for the parasite infectivity. This grant will investigate how mannogen is made and broken down by Leishmania. We will dissect exactly how enzymes, nature's catalysts, are used to make this energy store and see if the enzymes can be inhibited in order to provide the academic foundation for potential new anti-parasite agents. Around two million people each year contract this debilitating disease and around seventy thousand will die. Our research will provide insights into the metabolism into this major world parasite. Beyond this, our work shows that similar enzymes exist across bacteria, our work will probe their structure and function and hopefully identify new biochemical pathways in a range of bacteria.

大多数生物体以葡萄糖为基础的多糖的形式储存能量储备;例如，人类的糖原和植物中的淀粉。但有些生物使用更不寻常的碳水化合物储存形式。作为一个国际团队的一部分，我们刚刚发现了利什曼原虫-例如，白蛉传播利什曼病的病原体，以一种称为“甘露糖原”的不寻常多糖的形式储存能量。这种能量储存的形成对于寄生虫的感染性是必不可少的。这项补助金将调查利什曼原虫是如何制造和分解甘露醇的。我们将详细分析酶，自然界的催化剂，是如何被用来制造这种能量储存的，看看酶是否可以被抑制，以便为潜在的新的抗寄生虫剂提供学术基础。每年约有200万人感染这种使人衰弱的疾病，约有7万人死亡。我们的研究将提供深入了解这种主要世界寄生虫的代谢。除此之外，我们的工作表明，类似的酶存在于细菌中，我们的工作将探索它们的结构和功能，并希望在一系列细菌中发现新的生化途径。

项目成果

Structure, Function and Mechanism of N-Glycan Processing Enzymes: endo -a-1,2-Mannanase and endo -a-1,2-Mannosidase

N-聚糖加工酶的结构、功能和机制：内切-a-1,2-甘露聚糖酶和内切-a-1,2-甘露糖苷酶

• DOI: 10.1002/ijch.202200067
• 发表时间: 2022
• 期刊: Israel Journal of Chemistry
• 影响因子: 3.2
• 作者: Burchill L