期刊
CHEMCATCHEM
卷 14, 期 6, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cctc.202101648
关键词
biocatalysis; cytochrome P450; docking; enzyme engineering; molecular dynamics
资金
- Czech Ministry of Education [CZ.02.1.01/0.0/0.0/16_026/0008451, CZ.02.1.01/0.0/0.0/17_043/0009632, LM2018121]
- Projekt DEAL
The catalytic space of the P450 monooxygenase CYP153A(M.aq) was transformed from a fatty acid hydroxylase to a catalyst capable of omega-hydroxylation of dodecylamine. A rapid screening method called RAPP was established to measure saturation libraries directly from a 96-deepwell plate. Molecular modeling and dynamics simulations revealed significant effects of the mutations on the substrate tunnel architectures.
The catalytic space of the P450 monooxygenase CYP153A(M.aq) was opened from a terminal (omega-) fatty acid hydroxylase to a catalyst capable of performing omega-hydroxylation of dodecylamine, which is a potent inhibitor for the wild-type enzyme. A simple screening method named Rapid-flow Analysis of Product Peaks (RAPP) was established and applied to measure saturation libraries directly from a 96-deepwell plate in 36 seconds per sample. The obtained variants are less inhibited by the amine, although concurrently show less affinity towards the acid. Molecular modelling and molecular dynamics simulations showed significant effects of the mutations on the substrate tunnel architectures.
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