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

目前用作抗癌和抗生素的许多生物活性天然产物都是糖基化的。这些分子中碳水化合物部分的存在对它们的药用活性至关重要。产生天然产物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，它负责制造不寻常的糖，并最终附着在各种来源的天然产物苷元上（例如聚酮和非核糖体肽）。这些酶的催化机制和结构结构的详细阐明构成了开发新型生物催化剂和新型合成生物学方法的基础，这些方法可以产生“非自然”产品-这些分子仍然是生物合成的，但结构上多样化（例如，不同的糖基化），与原始对应物不同，可能具有优越的价值。本博士项目的目的是阐明参与罕见天然产物糖基化的生物合成酶的功能和结构。这项工作的结果将构成开发新的生物催化途径，以多样化的天然产物的基础。

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.