Engineering CYP153A M.aq to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening

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چکیده

The catalytic space of the P450 monooxygenase CYP153AM.aq was opened from a terminal (ω-) fatty acid hydroxylase to catalyst capable performing ω-hydroxylation dodecylamine, which is potent inhibitor for wild-type enzyme. A simple screening method named Rapid-flow Analysis Product Peaks (RAPP) established and applied measure saturation libraries directly 96-deepwell plate in 36 seconds per sample. obtained variants are less inhibited by amine, although concurrently show affinity towards acid. Molecular modelling molecular dynamics simulations showed significant effects mutations on substrate tunnel architectures.

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ژورنال

عنوان ژورنال: Chemcatchem

سال: 2022

ISSN: ['1867-3899', '1867-3880']

DOI: https://doi.org/10.1002/cctc.202101648