Project title: Refining oxidative enzyme systems from talented microorganisms for industrial biocatalysis

项目名称：从优秀微生物中精炼氧化酶系统用于工业生物催化

• 批准号: 132125
• 金额: $ 11.14万
• 依托单位: HYPHA DISCOVERY LIMITED
• 依托单位国家: 英国
• 项目类别: Feasibility Studies
• 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=132125
• 关键词: Project; title; Refining; oxidative; enzyme

Microorganisms and their cytochrome P450 (CYP) oxidative enzymes can be used for production of drugand agrochemical metabolites, or to produce new derivatives of early-stage lead compounds withimproved properties. Hypha Discovery’s panel of wild-type bacteria is highly effective in producingoxidized metabolites by whole-cell biotransformation but has limitations with regard to the speed andspecificity of production. This challenge will be addressed in collaboration with UCL by introducingindividual CYP enzymes from the six most talented members of the panel into E. coli and S. lividanschassis as three-gene operons using ferredoxin and ferredoxin reductase genes with broad functionalactivity. The catalytic activities of the resulting recombinant strains will be compared with those of thewild-type parents by testing against a diverse substrate panel. Cell-free enzyme extract preparations willthen be prepared and assembled into a kit that can be used for testing in client laboratories.

微生物及其细胞色素P450 （CYP）氧化酶可用于生产药物和农用化学品代谢物，或生产具有改进性能的早期先导化合物的新衍生物。Hypha Discovery的野生型细菌小组在通过全细胞生物转化生产氧化代谢物方面非常有效，但在生产速度和特异性方面存在局限性。这一挑战将与UCL合作解决，通过使用具有广泛功能活性的铁氧还蛋白和铁氧还蛋白还原酶基因，将小组中六位最有才华的成员的单个CYP酶引入大肠杆菌和葡萄球菌，作为三基因操纵子。重组菌株的催化活性将通过对不同底物面板的测试与野生型亲本的催化活性进行比较。然后制备无细胞酶提取物制剂并组装成可用于客户实验室检测的试剂盒。