Monooxygenase-Mediated Baeyer−Villiger Oxidations

Mihovilovič, Marko D.; Müller, Bernhard; Stanetty, Peter

doi:10.1002/1099-0690(200211)2002:22<3711::aid-ejoc3711>3.0.co;2-5

Cited by 236 publications

(103 citation statements)

References 130 publications

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“…This reaction is widely used to study the ability of BVMOs to carry out the kinetic resolution of racemic compounds, [18] and it is of interest for the synthesis of prostaglandins,f or example. [19] Small-scale conversions of rac-bicyclo[3.2.0]hept-2-en-6-one were carried out with TmCHMO,A cCHMO,a nd TfPAMO.B oth enantiomers of this ketone were fully converted by both CHMOs,y ielding almost exclusively one regioisomer from each enantiomer ( Figure S6A and Table S6). [20] By contrast, TfPAMO produced all four possible lactones,p roving to be far less regioselective than CHMOs.W ea lso used the same BVMOs to produce enantiomerically pure sulfoxides,w hich are widely used in asymmetric synthesis and are often biologically active.…”

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confidence: 99%

Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase

et al. 2016

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Cyclohexanone monooxygenase (CHMO) is ap romising biocatalyst for industrial reactions owing to its broad substrate spectrum and excellent regio-, chemo-, and enantioselectivity.However,the lowstability of many BaeyerVilliger monooxygenases is an obstacle for their exploitation in industry.C haracterization and crystal structure determination of ar obust CHMO from Thermocrispum municipale is reported. The enzyme efficiently converts avariety of aliphatic, aromatic,a nd cyclic ketones,a sw ell as prochiral sulfides.A compact substrate-binding cavity explains its preference for small rather than bulky substrates.S mall-scale conversions with either purified enzyme or whole cells demonstrated the remarkable properties of this newly discovered CHMO.T he exceptional solvent tolerance and thermostability make the enzyme very attractive for biotechnology.

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Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase

et al. 2016

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“…BVMOs are promising targets for biocatalytic applications in synthetic and pharmaceutical chemistry (11,12). Phenylacetone monooxygenase (PAMO, EC 1.14.13.92) from Thermobifida fusca features several attractive properties: it is thermostable, tolerant to organic solvents (13,14), and catalyzes enantioselective Baeyer-Villiger oxidations and sulfoxidations on a number of substrates in addition to phenylacetone (15).…”

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Snapshots of Enzymatic Baeyer-Villiger Catalysis

Orrù

Dudek

Martinoli

et al. 2011

Journal of Biological Chemistry

122

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Baeyer-Villiger monooxygenases catalyze the oxidation of carbonylic substrates to ester or lactone products using NADPH as electron donor and molecular oxygen as oxidative reactant. The emerging picture is that these enzymes are mainly oxygen-activating and "Criegee-stabilizing" catalysts that act on any chemically suitable substrate that can diffuse into the active site, emphasizing their potential value as toolboxes for biocatalytic applications.

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“…Baeyer-Villiger monooxygenases are classified depending on the nature of their flavin cofactor (4). The type I enzymes are the most extensively investigated (5). They are FAD-dependent proteins that use NADPH and molecular oxygen to insert an oxygen atom into their substrate.…”

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Crystal structure of a Baeyer–Villiger monooxygenase

Malito

Alfieri²,

Fraaije³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

280

305

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Flavin-containing Baeyer-Villiger monooxygenases employ NADPH and molecular oxygen to catalyze the insertion of an oxygen atom into a carbon-carbon bond of a carbonylic substrate. These enzymes can potentially be exploited in a variety of biocatalytic applications given the wide use of Baeyer-Villiger reactions in synthetic organic chemistry. The catalytic activity of these enzymes involves the formation of two crucial intermediates: a flavin peroxide generated by the reaction of the reduced flavin with molecular oxygen and the ''Criegee'' intermediate resulting from the attack of the flavin peroxide onto the substrate that is being oxygenated. The crystal structure of phenylacetone monooxygenase, a Baeyer-Villiger monooxygenase from the thermophilic bacterium Thermobifida fusca, exhibits a two-domain architecture resembling that of the disulfide oxidoreductases. The active site is located in a cleft at the domain interface. An arginine residue lays above the flavin ring in a position suited to stabilize the negatively charged flavin-peroxide and Criegee intermediates. This amino acid residue is predicted to exist in two positions; the ''IN'' position found in the crystal structure and an ''OUT'' position that allows NADPH to approach the flavin to reduce the cofactor. Domain rotations are proposed to bring about the conformational changes involved in catalysis. The structural studies highlight the functional complexity of this class of flavoenzymes, which coordinate the binding of three substrates (molecular oxygen, NADPH, and phenylacetone) in proximity of the flavin cofactor with formation of two distinct catalytic intermediates.flavoenzyme ͉ mechanism of catalysis ͉ biocatalysis ͉ Baeyer-Villiger reaction ͉ crystallography A t the end of the 19th century, Baeyer and Villiger (1) discovered that cyclic ketones react with oxidants, such as peroxymonosulfuric acid, to yield lactones. The mechanism of the Baeyer-Villiger reaction involves a nucleophilic attack of a peroxide to the ketone reagent to generate the so-called ''Criegee'' intermediate ( Fig. 1), which is followed by an intramolecular rearrangement that leads to the migration of an alkyl group to an oxygen atom, generating the lactone product. Baeyer-Villiger reactions are of enormous value in synthetic organic chemistry, and the number of their applications is countless.Several microorganisms produce enzymes capable to catalyze Baeyer-Villiger reactions. These proteins are extensively studied for their exploitation in biocatalytic applications (2, 3). This interest follows the problems related to the toxicity and instability of the oxidizing reactants that are currently being used in chemical processes. In addition, enzymatic reactions exhibit a superior degree of enantio-and regioselectivity. Baeyer-Villiger monooxygenases are classified depending on the nature of their flavin cofactor (4). The type I enzymes are the most extensively investigated (5). They are FAD-dependent proteins that use NADPH and molecular oxygen to insert an oxygen atom into th...

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Monooxygenase-Mediated Baeyer−Villiger Oxidations

Cited by 236 publications

References 130 publications

Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase

Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase

Snapshots of Enzymatic Baeyer-Villiger Catalysis

Crystal structure of a Baeyer–Villiger monooxygenase

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