Baeyer-Villiger monooxygenases types

Reagents (i) Wild-type Baeyer-Villiger monooxygenase CHMO from Adnetobacterap. NCIB 9871,... 

The first indication of the existence of so-called Baeyer-Villiger monooxygenases (BVMOs) was reported in the late 1940s [56]. It was observed that certain fungi were able to oxidize steroids via a BV reaction [56], but two decades elapsed before the first BVMOs were isolated and characterized [57, 58]. All characterized BVMOs contain a flavin cofactor that is vital for the catalytic activity of the enzyme, Furthermore, NADH or NADPH cofactors are needed as electron donors. Careful inspection of all available biochemical data on BVMOs has revealed that at least two discrete classes of BVMOs exist, types I and II [59]. 

Scheme 3.17 Artificial metabolic pathway composed by an alcohol dehydrogenase (LK-ADH), an enoate reductase (XenB), and a Baeyer-Villiger monooxygenase (BVMO j gj ) different substrate types that have been successfully converted to chiral products via this pathway.

A. Riebel, M.. Fink, M.D. Mihovilovic, M.W. Fraaije, Type II flavin-containing monooxygenases a new class of biocatalysts that harbors Baeyer-Villiger monooxygenases with a relaxed coenzyme specificity, ChemCatChem. 6 (2014) 1112-1117. 

SCHEME 36.12. Catalytic mechanism of type 1 Baeyer-Villiger monooxygenases for the BVO of cyclohexanone 30. 

Several types of flavoprotein monooxygenases exist. One group catalyzes electrophilic aromatic substitution or heteroatom oxidation reactions, whereas the other group catalyzes Baeyer-Villiger-type oxidations of ketones (Fig. 2) (13, 17). 

Monooxygenases carry out a Baeyer-Villiger-type reaction in the introduction of a single atom of oxygen into cycloalkanones with the production of lactones. Examples are given in Chapter 6, Section 6.1.2. 

Reetz and co-workers have demonstrated that the methods of directed evolution can be applied successfully to the creation of enantioselective cyclohexanone monooxygenases (CHMOs) as catalysts in Baeyer-Villiger reactions of several different substrates, for which the enantioselectivity ranges between 90-99% [100]. Ketone 5 gives a very poor enantioselectivety (9% ee, R-selective) with the wild-type CHMO. The enantioselectivety for 5 was significantly improved by directed evolution, and an S-selective variant gave 79% ee (Scheme 10.1). 

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