Baeyer-Villiger monooxygenases: From protein engineering to biocatalytic applications

Schmidt, Sandy; Bornscheuer, Uwe T.

doi:10.1016/bs.enz.2020.05.007

Cited by 18 publications

(11 citation statements)

References 174 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 13 , 14 A “greener” and a catalytic alternative is the use of Baeyer–Villiger monooxygenases (BVMOs). 15 These enzymes require nicotinamide and flavin cofactors (nicotinamide adenine dinucleotide, NADPH, and flavin adenine dinucleotide, FAD) and aerial oxygen to perform Baeyer–Villiger oxidations. BVMOs are outperforming traditional catalysis due to their excellent chemo-, regio-, and enantioselectivity.…”

mentioning

confidence: 99%

Mutations Increasing Cofactor Affinity, Improve Stability and Activity of a Baeyer–Villiger Monooxygenase

et al. 2022

View full text Add to dashboard Cite

The typically low thermodynamic and kinetic stability of enzymes is a bottleneck for their application in industrial synthesis. Baeyer–Villiger monooxygenases, which oxidize ketones to lactones using aerial oxygen, among other activities, suffer particularly from these instabilities. Previous efforts in protein engineering have increased thermodynamic stability but at the price of decreased activity. Here, we solved this trade-off by introducing mutations in a cyclohexanone monooxygenase from Acinetobacter sp., guided by a combination of rational and structure-guided consensus approaches. We developed variants with improved activity (1.5- to 2.5-fold) and increased thermodynamic (+5 °C T m ) and kinetic stability (8-fold). Our analysis revealed a crucial position in the cofactor binding domain, responsible for an 11-fold increase in affinity to the flavin cofactor, and explained using MD simulations. This gain in affinity was compatible with other mutations. While our study focused on a particular model enzyme, previous studies indicate that these findings are plausibly applicable to other BVMOs, and possibly to other flavin-dependent monooxygenases. These new design principles can inform the development of industrially robust, flavin-dependent biocatalysts for various oxidations.

show abstract

mentioning

confidence: 99%

Mutations Increasing Cofactor Affinity, Improve Stability and Activity of a Baeyer–Villiger Monooxygenase

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Since the first crystal structure of a type I BVMO (i.e. phenylacetone monooxygenase (PAMO); EC 1.14.13.92) was elucidated in 2004 [67], the number of studies about the production, engineering, and biocatalytic properties of BVMOs has exploded [65,[68][69][70][71]. Next to the discovery and characterization of new members [72][73][74], close attention was paid to improving the substrate scope and thermal stability of BVMOs [10, [75][76][77][78][79][80][81].…”

Section: Group B Reactionsmentioning

confidence: 99%

Flavoprotein Monooxygenases and Halogenases

Paul

Guarneri

Berkel

2021

Flavin‐Based Catalysis

View full text Add to dashboard Cite

Article 25fa states that the author of a short scientific work funded either wholly or partially by Dutch public funds is entitled to make that work publicly available for no consideration following a reasonable period of time after the work was first published, provided that clear reference is made to the source of the first publication of the work.This publication is distributed under The Association of Universities in the Netherlands (VSNU) 'Article 25fa implementation' project. In this project research outputs of researchers employed by Dutch Universities that comply with the legal requirements of Article 25fa of the Dutch Copyright Act are distributed online and free of cost or other barriers in institutional repositories. Research outputs are distributed six months after their first online publication in the original published version and with proper attribution to the source of the original publication.

show abstract

“…In this area, oxidoreductases are enzymes frequently used in cascade reactions, as usually a pair of these enzymes are simultaneously applied for the required in situ recycling of the cofactors [12][13][14][15]. Inside this type of enzymes, Baeyer-Villiger monooxygenases (BVMOs) are undoubtedly one of the most attractive members of this family; these flavin-dependent oxidative enzymes [16][17][18][19][20] are capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp 2 and the Csp 3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones [20][21][22][23][24][25][26][27], as schematized in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases

Gonzalo

Alcántara

2021

Catalysts

View full text Add to dashboard Cite

Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the recent advances for overcoming the drawbacks of using BVMOs in these techniques.

show abstract

Baeyer-Villiger monooxygenases: From protein engineering to biocatalytic applications

Cited by 18 publications

References 174 publications

Mutations Increasing Cofactor Affinity, Improve Stability and Activity of a Baeyer–Villiger Monooxygenase

Mutations Increasing Cofactor Affinity, Improve Stability and Activity of a Baeyer–Villiger Monooxygenase

Flavoprotein Monooxygenases and Halogenases

Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases

Contact Info

Product

Resources

About