Functional expression and activity screening of all human cytochrome P450 enzymes in fission yeast

FEBS Letters

article

Pradeepraj Durairaj¹  Linbing Fan¹  Wei Du¹  Shabir Ahmad¹  Dawit Mebrahtu¹  Shishir Sharma¹  Rana Azeem Ashraf¹  Jiaxin Liu¹  Qian Liu¹  Matthias Bureik¹ 

[1] School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University

关键词: cytochrome P450;    fission yeast;    functional expression;    gene library;    Homo sapiens;    pharmacology;   

DOI  :  10.1002/1873-3468.13441

来源: John Wiley & Sons Ltd.

【 摘 要 】

Here, a complete set of recombinant fission yeast strains that coexpress each of the 57 human cytochrome P450 (CYP) enzymes together with their natural human electron transfer partner(s) was cloned. This strain collection was tested with two luminogenic probe substrates, and 31 human CYPs (including the orphan enzymes CYP2A7, CYP4A22 and CYP20A1) were found to metabolize at least one of these. Since other substrates are known for the remaining enzymes, all human CYPs are now shown to be active. Interestingly, CYP5A1 was found for the first time to work on a substrate other than prostaglandin H2, and, moreover, to catalyze an aliphatic hydroxylation reaction that consumes molecular oxygen. Also, the ability of CYP11A1 to catalyze an aryl hydroxylation is another unexpected result.

【 授权许可】

Unknown