Enzymatic Investigations in Gentamicin C Biosynthesis

庆大霉素 C 生物合成的酶学研究

• 批准号: 1804949
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1804949
• 关键词: Enzymatic; Investigations; Gentamicin; Biosynthesis

Theme: Industrial Biotechnology and BioenergyThe inevitable approach of the post-antibiotic era has focussed attention on the revamp of established antibacterial agents in order to attain more robust variants. Re-engineering the biosynthetic pathway of a natural product-derived antibiotic is an attractive alternative to semisynthetic approaches; a prerequisite for this is cognizance of the complete biosyntheticenzymology.This project will endeavour to explore the substrate specificity of the aminotransferases GenB1, GenB2, GenB3 and GenB4involved in the distinctive 3',4'-bisdehydroxylation process in gentamicin biosynthesis, by functional enzyme studies usingsubstrate analogs. This would enable efforts to rationally manipulate the enzymatic transformations which is a prerequisitefor the task of redirecting the course of the biosynthetic pathway to obtain a defined composition of end-product. Likewise, engineering the substrate specificity of the dehydrogenase GenQ will need to be undertaken to contribute to the accomplishment of such an aim. Previous studies concerning the JI-20B/JI20Ba epimer pair - on the determination of configuration at the chiral C-6 position - will also be concluded.

布景主题：工业生物技术和生物能源后抗生素时代不可避免的方法已经将注意力集中在对现有抗菌剂的改造上，以获得更强大的变体。重新设计天然产物衍生抗生素的生物合成途径是半合成方法的一种有吸引力的替代方法;本项目将致力于探索庆大霉素生物合成中独特的3 ′，4 ′-双脱羟基化过程中所涉及的氨基转移酶GenB 1、GenB 2、GenB 3和GenB 4的底物特异性，by functional功能enzyme酶studies研究using使用substrate底物analogs类似物.这将使合理地操纵酶促转化的努力成为可能，这是重定向生物合成途径的过程以获得最终产物的确定组成的任务的先决条件。同样，需要对脱氢酶GenQ的底物特异性进行工程改造，以有助于实现这一目标。还将总结关于JI-20 B/JI 20 Ba差向异构体对的先前研究-关于手性C-6位置处构型的确定。