The mutagenesis of a single site for enhancing or reversing the enantio- or regiopreference of cyclohexanone monooxygenases

Abstract

<p>The mutagenesis of a “second sphere” switch residue of CHMOAcineto could control its enantio- and regiopreference. Replacing phenylalanine (F) at position 277 of CHMOAcineto into larger tryptophan (W) enabled a...</p>

Structure-guided semi-rational design of an imine reductase for enantio-complementary synthesis of pyrrolidinamine

“…34–38 Rational design usually focuses on a minority of potential amino acids, which can significantly reduce the number of mutants to be investigated. 37,38 Although several advances focusing on tuning enzymatic catalytic efficiency have been reported, 26,28,29 rational design of IREDs for stereo-divergent reductive amination to synthesize both stereoisomers is relatively undeveloped.…”

“…26,28,29 Alternatively, rationally engineering an enzyme, which shows high catalytic efficiency for target substrates, to obtain enantio-preference enzymes is a highly efficient method. [34][35][36][37][38] Rational design usually focuses on a minority of potential amino acids, which can signicantly reduce the number of mutants to be investigated. 37,38 Although several advances focusing on tuning enzymatic catalytic efficiency have been reported, 26,28,29 rational design of IREDs for stereo-divergent reductive amination to synthesize both stereoisomers is relatively undeveloped.…”

Redesigning Enzymes for Biocatalysis: Exploiting Structural Understanding for Improved Selectivity

“…Surprisingly, a single phenylalanine residue determines selectivity among CHMOs. Mutagenesis of this conserved phenylalanine close to the binding pocket in CHMOs predictably changes the regioselectivity of lactone formation (Hu et al, 2020). The approach of targeting large hydrophobic residues and mutating them to reduce the steric bulk and hydrophobicity in an active site, can hold for a variety of enzymes even on large complex molecules.…”

Colorimetric High‐Throughput Screening Method for Directed Evolution of Prazole Sulfide Monooxygenase

“…[2] In addition to their use for synthesis of esters or lactones from ketones, several BVMOs can be used for the synthesis of chiral sulfoxides. [3,4] Proton pump inhibitors (PPIs) are sulfoxide-type drugs that are used to treat gastrointestinal diseases. [5] BVMO-mediated asymmetric sulfoxidation of prazole sulfides under environmentally friendly conditions has been reported as an attractive green alternative to conventional chemical synthesis (Scheme 1).…”

“…1.14.13.x), which are named for their important role in catalyzing Baeyer‐Villiger oxidation reactions, [1] are becoming an effective alternative to metal‐based chemical catalysts [2] . In addition to their use for synthesis of esters or lactones from ketones, several BVMOs can be used for the synthesis of chiral sulfoxides [3,4] . Proton pump inhibitors (PPIs) are sulfoxide‐type drugs that are used to treat gastrointestinal diseases [5] .…”