Snapshots of Enzymatic Baeyer-Villiger Catalysis

Orrù, Roberto; Dudek, Hanna M.; Martinoli, C.; Pazmiño, Daniel E. Torres; Royant, Antoine; Weik, Martin H.; Fraaije, Marco W.; Mattevi, Andrea

doi:10.1074/jbc.m111.255075

Cited by 118 publications

(94 citation statements)

References 39 publications

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“…50 Here, we showed that the positively charged His396 of C 2 acts as a general acid for proton-coupled electron transfer to activate O 2 . Another enzyme that catalyzes the same reaction as the C 2 , the oxygenase component of 4-hydroxyphenylacetate 3-monooxygenasefrom Thermus thermophilus HB8 (HpaB), 51 has an Arg residue (Arg100) located ~4.8 Å from C4a.…”

Section: Discussionmentioning

confidence: 95%

Mechanism of Oxygen Activation in a Flavin-Dependent Monooxygenase: A Nearly Barrierless Formation of C4a-Hydroperoxyflavin via Proton-Coupled Electron Transfer

et al. 2015

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Understanding how flavin-dependent enzymes activate oxygen for their oxidation and oxygenation reactions is one of the most challenging issues in flavoenzymology. Density functional calculations and transient kinetics were performed to investigate the mechanism of oxygen activation in the oxygenase component (C2) of p-hydroxyphenylacetate 3-hydroxylase (HPAH). We found that the protonation of dioxygen by His396 via a proton-coupled electron transfer mechanism is the key step in the formation of the triplet diradical complex of flavin semiquinone and (•)OOH. This complex undergoes intersystem crossing to form the open-shell singlet diradical complex before it forms the closed-shell singlet C4a-hydroperoxyflavin intermediate (C4aOOH). Notably, density functional calculations indicated that the formation of C4aOOH is nearly barrierless, possibly facilitated by the active site arrangement in which His396 positions the proximal oxygen of the (•)OOH in an optimum position to directly attack the C4a atom of the isoalloxazine ring. The nearly barrierless formation of C4aOOH agrees well with the experimental results; based on transient kinetics and Eyring plot analyses, the enthalpy of activation for the formation of C4aOOH is only 1.4 kcal/mol and the formation of C4aOOH by C2 is fast (∼10(6) M(-1) s(-1) at 4 °C). The calculations identified Ser171 as the key residue that stabilizes C4aOOH by accepting a hydrogen bond from the H(N5) of the isoalloxazine ring. Both Ser171 and Trp112 facilitate H2O2 elimination by donating hydrogen bonds to the proximal oxygen of the OOH moiety during the proton transfer. According to our combined theoretical and experimental studies, the existence of a positively charged general acid at the position optimized for facilitating the proton-coupled electron transfer has emerged as an important catalytic feature for the oxygen activation process in flavin-dependent enzymes.

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Section: Discussionmentioning

confidence: 95%

Mechanism of Oxygen Activation in a Flavin-Dependent Monooxygenase: A Nearly Barrierless Formation of C4a-Hydroperoxyflavin via Proton-Coupled Electron Transfer

et al. 2015

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“…23 Following the publication of these three structures, reports of several more PAMO structures, in complex with NADP + as well as a weak inhibitor, were solved. 24 The PAMO structures allowed the comparison of the oxidized and reduced states of FAD. In addition, a series of structures of 2-oxo-Δ 3 -4,5,5-trimethylcyclopentenylacetyl-coenzyme A monooxygenase (OTEMO) 25 were solved, representing the first BVMO crystal structures of a dimeric BVMO, and also of a BVMO that acts on a very large substrate.…”

mentioning

confidence: 99%

Lactone-Bound Structures of Cyclohexanone Monooxygenase Provide Insight into the Stereochemistry of Catalysis

Yachnin

McEvoy

MacCuish³

et al. 2014

ACS Chem. Biol.

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NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/ctrl?action=rtdoc&an=21275605&lang=en http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/ctrl?action=rtdoc&an=21275605&lang=fr READ THESE TERMS AND CONDITIONS CAREFULLY BEFORE USING THIS WEBSITE.http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/jsp/nparc_cp.jsp?lang=en Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://doi.org/10.1021/cb500442e Chemical Biology, 9, 12, pp. 2843-2851, 2014 Lactone ABSTRACT: The Baeyer−Villiger monooxygenases (BVMOs) are microbial enzymes that catalyze the synthetically useful Baeyer−Villiger oxidation reaction. The available BVMO crystal structures all lack a substrate or product bound in a position that would determine the substrate specificity and stereospecificity of the enzyme. Here, we report two crystal structures of cyclohexanone monooxygenase (CHMO) with its product, ε-caprolactone, bound: the CHMO Tight and CHMO Loose structures. The CHMO Tight structure represents the enzyme state in which substrate acceptance and stereospecificity is determined, providing a foundation for engineering BVMOs with altered substrate spectra and/or stereospecificity. The CHMO Loose structure is the first structure where the product is solvent accessible. This structure represents the enzyme state upon binding and release of the substrate and product. In addition, the role of the invariant Arg329 in chaperoning the substrate/product during the catalytic cycle is highlighted. Overall, these data provide a structural framework for the engineering of BVMOs with altered substrate spectra and/or stereospecificity. ACS

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“…) readily perform such transformations lend to speculate that there are still more intricate details influencing BVMO promiscuity in the reaction mechanism [24] of the enzymatic Baeyer-Villiger oxidation that have not been understood so far.…”

Section: Scoring Results Of Bvmosmentioning

confidence: 97%

Quantitative Comparison of Chiral Catalysts Selectivity and Performance: A Generic Concept Illustrated with Cyclododecanone Monooxygenase as Baeyer–Villiger Biocatalyst

et al. 2012

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Within this work a generic tool for chiral catalyst evaluation is established based on the application-oriented properties activity and selectivity; the concept aims at quantitatively comparing catalyst performance in general on a multitude of substrates. It is designed and intended to serve as decision guidance for challenges in catalysis and comprehensible information extraction from already recorded but unrefined data sets. The underlying algorithm assigns function points to catalytic entities via a statistically solid model possessing high flexibility and generates a relative ranking. This is coupled to an automated iterative refinement process towards maximum information content of results employing Shannon entropy optimization. Consequently, the developed workflow facilitates high distinguishability between catalysts even in low-scattering data sets. The numerical ranking is complemented by a clearly arranged graphic representation permitting facile and reliable visual interpretation of generality or niche capabilities of catalysts. Usefulness of the title concept is demonstrated by the performance evaluation of cyclododecanone monooxygenase, a highly versatile Baeyer-Villiger enzyme. To retain broad applicability, an open-source MATLAB script is provided in electronic form.

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Snapshots of Enzymatic Baeyer-Villiger Catalysis

Cited by 118 publications

References 39 publications

Mechanism of Oxygen Activation in a Flavin-Dependent Monooxygenase: A Nearly Barrierless Formation of C4a-Hydroperoxyflavin via Proton-Coupled Electron Transfer

Mechanism of Oxygen Activation in a Flavin-Dependent Monooxygenase: A Nearly Barrierless Formation of C4a-Hydroperoxyflavin via Proton-Coupled Electron Transfer

Lactone-Bound Structures of Cyclohexanone Monooxygenase Provide Insight into the Stereochemistry of Catalysis

Quantitative Comparison of Chiral Catalysts Selectivity and Performance: A Generic Concept Illustrated with Cyclododecanone Monooxygenase as Baeyer–Villiger Biocatalyst

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