Biocatalyst parts evaluation and pathway refactoring for synthetic drug manufacture

该项目涉及利用合成生物学开发生产高价值治疗化合物的可持续制造平台的必要性。这里的重点是大麻素类化合物和相关化合物，它们是越来越多的长期疾病状态(例如多发性硬化症和控制失控肌肉痉挛)的有吸引力的治疗目标。出于这一目的，受到严格监管的纯形式大麻类药物的市场日益增长。合成生物学平台现在提供了机会，为生产适合的宿主菌株的大麻素提供制造管道，以实现可持续的合成。该项目将利用我们现有的萜类平台来支持合成新的目标化合物，并使用合成生物学方法从现有的和新获得的编码生物催化部分的基因中重构新的代谢途径。该项目涉及使用曼彻斯特合成生物学中心(SYNBIOCHEM)提供的高度自动化的合成生物学平台对这些化合物的生物催化部分和途径进行详细的结构、生物催化和酶学表征。候选人将致力于这些化合物的合成所涉及的酶的生化、结构和工程方面的工作，以及为其生物合成组装多个途径和调节工具。该学生将在蛋白质生产、结构生物学、生物催化、诱变和当代合成生物学方法方面发展专业知识，为化学品生产建立代谢途径。

The project is concerned with the need to develop sustainable manufacturing platforms for the production of high value therapeutic compounds using synthetic biology. The focus here is on cannibinoids and related compounds, which are attractive targets for therapy in a growing number of long term disease states (e.g. multiple sclerosis and the control of uncontrolled muscle spasms). There is a growing market for tightly regulated and pure forms of cannabinoids for this purpose. Synthetic biology platforms now provide the opportunity to develop manufacturing pipelines for cannabinoid production in suitable host strains for the purposes of sustainable synthesis. The project will make use of our existing terpene platforms to support the synthesis of the new target compounds and the refactoring of new metabolic pathways using synthetic biology approaches from existing and newly sourced genes that encode biocatalytic parts.The project involves the detailed structural, biocatalytic and enzymological characterisation of biocatalytic parts and pathways for these compounds using the highly automated synthetic biology platforms available in the Manchester Synthetic Biology Centre (SYNBIOCHEM). The candidate will work on the biochemical and structural and engineering aspects of enzymes involved in the synthesis of these compounds and the assembly of multiple pathways and regulatory tools for their biosynthesis.The student will develop expertise in protein production, structural biology, biocatalysis, mutagenesis and contemporary synthetic biology approaches in building metabolic pathways for chemicals production.