Functional and structural characterisation of unusual carbohydrate-processing enzymes in natural product biosynthesis

天然产物生物合成中异常碳水化合物加工酶的功能和结构表征

• 批准号: 2097369
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2097369
• 关键词: Functional; structural; characterisation; unusual; carbohydrate

Many bioactive natural products currently utilised as anticancer and antibiotic agents are glycosylated. The presence of carbohydrate moieties in these molecules is essential to their medicinal activity. Microorganisms that produce natural products harbor innumerous intriguing carbohydrate- processing enzymes, including glycosyltransferases, which are responsible for the making of unusual sugars and their ultimate attachment to natural product aglycones of various origins (e.g. polyketides and nonribosomal peptides). The detailed elucidation of these enzymes catalytic mechanisms and structural architecture constitutes the basis for the development of novel biotacalysts and of novel synthetic biology approaches towards the generation of 'unnatural' products- molecules that are still produced biosynthetically but that are structurally diversified (e.g. differently glycosylated) from their original counterparts, and may be of superior value.The aim of this PhD project is to elucidate the function and the structure of biosynthetic enzymes involved in unusual natural product glycosylation. The outcomes of this work will constitute the basis for the development of novel biocatalytic routes to diversified natural products.

许多目前用作抗癌剂的生物活性天然产品都是糖基化的。这些分子中碳水化合物部分的存在对于它们的药物活性至关重要。生产天然产物的微生物具有无数吸引人的碳水化合物加工酶，包括糖基转移酶，这些酶负责制造异常糖及其对各种起源的天然产物的最终附着（例如，多酮化合物和非脂质体肽）。这些酶催化机制和结构结构的详细阐明构成了新型生物构菌素的发展和新型合成生物学方法的基础，从而产生“不自然”的产物分子，这些分子仍然是生物合成的，但在结构上是不同的（例如，结构上有差异化的玻璃化玻璃化胶质糖囊囊酰基化） ）从其原始对应物中，并且该博士学位项目的目的是阐明与异常天然产物糖基化有关的生物合成酶的功能和结构。这项工作的结果将构成开发新的生物催化途径到多样化天然产品的基础。