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

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，或用于生产性能得到改善的早期铅化合物的新衍生物。菌丝发现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。这一挑战将与伦敦大学学院合作，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，将来自小组中最有才华的六名成员的单个CYP酶作为三基因操纵子引入大肠杆菌和利维丹链霉菌底盘。重组菌株的催化活性将与野生型亲本的催化活性进行比较，方法是在不同的底物板上进行测试。然后，将准备无细胞酶提取物制剂，并将其组装成可在客户实验室进行测试的试剂盒。

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.