Mechanical insights into the oxidative cleavage of resveratrol catalyzed by dioxygenase NOV1 from <i>Novosphingobium aromaticivorans</i>: confirmation of dioxygenase mechanism by QM/MM calculations

Bai, Jie; Hou, Qianqian; Zhu, Weiping; Liu, Yongjun

doi:10.1039/c8cy01885e

Cited by 21 publications

(28 citation statements)

References 49 publications

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“…9). In the study by Bai et al, the initial reactive species was identified as an end-on Fe III -O 2 − complex with a triplet or quintet spin state [77]. The lowest energy barrier reaction pathway involved attack of the activated oxygen on the α-carbon of resveratrol to generate a resonance-stabilized free radical involving the 4'-hydroxyl group.…”

Section: Computational Studiesmentioning

confidence: 99%

Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs)

Daruwalla

Kiser

2020

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Section: Computational Studiesmentioning

confidence: 99%

Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs)

Daruwalla

Kiser

2020

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…However, the β,β-carotenoid-cleaving enzyme BCO2 also has conserved Phe residues at these positions, indicating that other factors also determine whether bicyclic carotenoids are accepted or excluded. The scissile bond is oriented with respect to the metal center such that an end-on bound O 2 molecule, modeled as suggested from computational studies (49,50), would be well aligned with the C14′-C13′ bond for dioxetane formation (Fig. 7 A and B).…”

Section: Distribution Of Ccds In Archaeamentioning

confidence: 98%

“…Dissociation of the aquo ligand may be promoted by its close interaction with the apocarotenoid. III, The aquo ligand is replaced by O 2 , with simultaneous electron transfer from the apocarotenoid to the iron-oxy complex, an intermediate suggested by computational studies(49,50). The negative surface potential (red color) may help to stabilize the cationic intermediate formed during this step.…”

mentioning

confidence: 99%

Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Daruwalla

Zhang

Lee

et al. 2020

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

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Apocarotenoids are important signaling molecules generated from carotenoids through the action of carotenoid cleavage dioxygenases (CCDs). These enzymes have a remarkable ability to cleave carotenoids at specific alkene bonds while leaving chemically similar sites within the polyene intact. Although several bacterial and eukaryotic CCDs have been characterized, the long-standing goal of experimentally visualizing a CCD–carotenoid complex at high resolution to explain this exquisite regioselectivity remains unfulfilled. CCD genes are also present in some archaeal genomes, but the encoded enzymes remain uninvestigated. Here, we address this knowledge gap through analysis of a metazoan-like archaeal CCD from Candidatus Nitrosotalea devanaterra (NdCCD). NdCCD was active toward β-apocarotenoids but did not cleave bicyclic carotenoids. It exhibited an unusual regiospecificity, cleaving apocarotenoids solely at the C14′–C13′ alkene bond to produce β-apo-14′-carotenals. The structure of NdCCD revealed a tapered active site cavity markedly different from the broad active site observed for the retinal-forming Synechocystis apocarotenoid oxygenase (SynACO) but similar to the vertebrate retinoid isomerase RPE65. The structure of NdCCD in complex with its apocarotenoid product demonstrated that the site of cleavage is defined by interactions along the substrate binding cleft as well as selective stabilization of reaction intermediates at the scissile alkene. These data on the molecular basis of CCD catalysis shed light on the origins of the varied catalytic activities found in metazoan CCDs, opening the possibility of modifying their activity through rational chemical or genetic approaches.

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“…323 Three other CAOs functioning as stilbene cleavage oxygenases (SCOs) have recently been functionally characterized from Aspergillus fumigatus, Chaetomium globosum and Botryotinia fuckeliana 324 as well as a resveratrol cleaving dioxygenase NOV1 from Novosphingobium aromaticivorans. 325,326 Insert Figure 10 Many degradation pathways of stilbene phytoalexins have been described in fungi involving deglucosylation, dimerization and oxidation reactions leading to lactones or aldehydes. It is thus difficult to draw conclusions as to define a general mechanism for stilbene catabolism in fungi.…”

Section: Fungal Catabolism Of Stilbenesmentioning

confidence: 99%