Evolution study of the Baeyer–Villiger monooxygenases enzyme family: Functional importance of the highly conserved residues

Baeyer–Villiger monooxygenases (BVMOs) catalyze the transformation of linear and cyclic ketones into their corresponding esters and lactones by introducing an oxygen atom into a C–C bond. This bioreaction has numerous advantages compared to its chemical version; it does not induce the use of potentially harmful reagents (i.e., green chemistry) and displays significant better enantio- and regio-selectivity. New potential BVMOs were searched using sequence homology for type I BVMO proteins. 116 new sequences were identified as new putative BVMOs respecting the defined selection criteria. Multiple sequence alignments were carried out on the selected sequences to study the conservation of structurally and/or functionally important amino acids during evolution. Type I BVMO signature motif was found to be conserved in 94.8% of the sequences. We noticed also the highly conserved – but previously unnoticed – Threonine 167 (93.1%), located in the signature motif; this position could be added in the pattern used to characterize specific Type I enzymes. Amino acids at the vicinity of the FAD and NADPH cofactors were found also to be highly conserved and the details of the interactions were emphasized. Interestingly, residues at the enzyme binding site were found less conserved in terms of sequence evolution, leading sometimes to some important amino acid changes. These behaviors could explain the enzyme selectivity and specificity for different ligands. [Display omitted] •Robust protocol to study residues conservation during evolution.•A new more elaborated type I BVMO signature motif.•FAD binding domain more conserved than NADPH binding domain.•Highlights of the interaction details between enzyme and both cofactors.