Flavoprotein Monooxygenases and Halogenases

Abstract

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The Unexplored Importance of Fleeting Chiral Intermediates in Enzyme-Catalyzed Reactions

“…Baeyer−Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that occur in many different organisms and plants. 43,44,[47][48][49]118 Decades of intense efforts have uncovered the general features of the mechanism. Flavin is first reduced by NADPH, which then reacts with molecular oxygen (O 2 ) to selectively form a Calkylhydroperoxide at the C4α position.…”

“…Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that occur in many different organisms and plants. ,,− , Decades of intense efforts have uncovered the general features of the mechanism. Flavin is first reduced by NADPH, which then reacts with molecular oxygen (O 2 ) to selectively form a C-alkylhydroperoxide at the C4α position. , The C4α stereochemistry, as opposed to the alternative C4ß configuration, was chosen on the basis of early indirect experimental evidence, and has never been questioned. ,, This intermediate then adds nucleophilically to the carbonyl function with formation of the tetrahedral Criegee-intermediate, which in the case of cyclohexanone is not chiral.…”

Indole and azaindole halogenation catalyzed by the RebH enzyme variant 3-LSR utilizing co-purified E. coli reductase

“…Stereo and regioselectivity is another challenge in many cases whereby a mixture of isomers is obtained. Enzymatic halogenation offers a highly attractive alternative, allowing green chemistry principles (van Pée, 2012;Schnepel and Sewald, 2017;Latham et al, 2018;Fejzagić et al, 2019;Crowe et al, 2021;Paul et al, 2021) such as less hazardous chemical synthesis and use of safer solvents. For example, the use of halogenases in aqueous reaction media at ambient temperatures minimizes the use of…”