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

目前被用作抗癌和抗生素的许多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它们的药用活性是必不可少的。产生天然产品的微生物含有无数有趣的碳水化合物加工酶，包括糖基转移酶，这些酶负责制造不寻常的糖并最终附着于各种来源的天然产品苷元(如聚酮和非核糖体肽)。对这些酶的催化机制和结构结构的详细阐述构成了开发新型生物催化剂和新的合成生物学方法的基础，以产生“非天然”产物--这些分子仍然是以生物合成的方式产生的，但结构多样化(例如，糖基化作用不同)，可能具有更高的价值。这个博士项目的目的是阐明参与不寻常的天然产物糖基化的生物合成酶的功能和结构。这项工作的结果将为开发新的生物催化路线以获得多样化的天然产品奠定基础。

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.