Side-Chain Pruning Has Limited Impact on Substrate Preference in a Promiscuous Enzyme.

ABSTRACT: Detoxifying enzymes such as flavin-containing monooxygenases deal with a huge array of highly diverse xenobiotics and toxic compounds. In addition to being of high physiological relevance, these drug-metabolizing enzymes are useful catalysts for synthetic chemistry. Despite the wealth of studies, the molecular basis of their relaxed substrate selectivity remains an open question. Here, we addressed this issue by applying a cumulative alanine mutagenesis approach to cyclohexanone monooxygenase from Thermocrispum municipale, a flavin-dependent Baeyer-Villiger monooxygenase which we chose as a model system because of its pronounced thermostability and substrate promiscuity. Simultaneous removal of up to eight noncatalytic active-site side chains including four phenylalanines had no eff

SUBMITTER: Furst MJLJ 

PROVIDER: S-EPMC6345240 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature