The Oxygenase CAO-1 of Neurospora crassa Is a Resveratrol Cleavage Enzyme

Díaz-Sánchez, Violeta; Estrada, Alejandro F.; Limón, M. Carmen; Al‐Babili, Salim; Ávalos, Javier

doi:10.1128/ec.00084-13

Cited by 24 publications

(36 citation statements)

References 65 publications

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“…Stilbene derivatives such as resveratrol are antimicrobials, and it is possible NOV1 plays a role in pathogen resistance to plant defenses. This role has been suggested for the SCO CAO-1 (6) from N. crassa. Little is known about this antimicrobial resistance pathway, and further research may have implications for the production of food crops.…”

Section: Discussionmentioning

confidence: 66%

Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase

McAndrew

Sathitsuksanoh

Mbughuni

et al. 2016

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

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Stilbenes are diphenyl ethene compounds produced naturally in a wide variety of plant species and some bacteria. Stilbenes are also derived from lignin during kraft pulping. Stilbene cleavage oxygenases (SCOs) cleave the central double bond of stilbenes, forming two phenolic aldehydes. Here, we report the structure of an SCO. The X-ray structure of NOV1 from Novosphingobium aromaticivorans was determined in complex with its substrate resveratrol (1.89 Å), its product vanillin (1.75 Å), and without any bound ligand (1.61 Å). The enzyme is a seven-bladed β-propeller with an iron cofactor coordinated by four histidines. In all three structures, dioxygen is observed bound to the iron in a side-on fashion. These structures, along with EPR analysis, allow us to propose a mechanism in which a ferric-superoxide reacts with substrate activated by deprotonation of a phenol group at position 4 of the substrate, which allows movement of electron density toward the central double bond and thus facilitates reaction with the ferric superoxide electrophile. Correspondingly, NOV1 cleaves a wide range of other stilbene-like compounds with a 4′-OH group, offering potential in processing some solubilized fragments of lignin into monomer aromatic compounds.tilbenes are diphenyl ethene compounds that are produced naturally in a wide variety of plant species and some bacteria. One stilbene derivative of note is resveratrol, which is a plant phytoalexin abundant in grapes and peanuts. Studies have demonstrated numerous health benefits related to the consumption of resveratrol, which is correlated with reduced cardiovascular disease and cancer (1). Lignostilbene α,β-dioxygenase (LSD, EC 1.13.11.43), originally observed in Sphingomonas paucimobilis, was the first enzyme shown to cleave the central double bond of stilbenes, forming two phenolic aldehydes (2, 3). Subsequently, NOV1 and NOV2 (4) from Novosphingobium aromaticivorans, Rco1 (5) from Ustilago maydis, and CAO-1 (6) from Neurospora crassa were also shown to be stilbene cleaving oxygenases (SCOs). SCOs are related to carotenoid cleavage oxygenases (CCOs), which are enzymes that oxidatively cleave β-carotene or apocarotenoids. Carotenoids are a diverse class of molecules that play important roles in photosynthesis, immune function, and light perception in the eye. CCOs have been studied in great detail, including several crystal structures (7-9).Here, we present the X-ray structure of an SCO, NOV1 from N. aromaticivorans (NOV1). The structure was determined in complex with a representative substrate (resveratrol), a representative product (vanillin), and without ligand bound. We have also observed the ternary complex with oxygen and substrate or product bound, which has not been previously detected in a crystal structure of any CCO-related enzyme. Despite being related to CCOs, this structure of NOV1 shows several key differences that are indicative of their disparate substrate specificities. Moreover, the observed placement of Fe, O 2 , and the phenolic substrate resveratrol in th...

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Section: Discussionmentioning

confidence: 66%

Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase

McAndrew

Sathitsuksanoh

Mbughuni

et al. 2016

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

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“…However, it could be due also to technical drawbacks, such as incorrect folding or insolubility. Interestingly, no retinal-forming enzyme has been found so far in N. crassa (Díaz-Sánchez et al, 2013), despite the ability of its rhodopsin NOP-1 to bind retinal in vitro (Bieszke et al, 1999b).…”

Section: Discussionmentioning

confidence: 99%

“…However, no retinal biosynthetic activity has been found so far in N. crassa, in spite of the presence of NOP-1 (Bieszke et al, 1999a), a photoactive rhodopsin for which the ability to bind retinal has been demonstrated in vitro (Bieszke et al, 1999b). The putative retinal-forming enzyme of N. crassa, the oxygenase CAO-1, is unable to cleave -carotene but it efficiently cleaves resveratrol (Díaz-Sánchez et al, 2013), a biphenolic phytoalexin produced by some plants.…”

Section: Introductionmentioning

confidence: 99%

A RALDH-like enzyme involved in Fusarium verticillioides development

Díaz-Sánchez

Limón

Schaub

et al. 2016

Fungal Genetics and Biology

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Please cite this article as: Díaz-Sánchez, V., Carmen Limón, M., Schaub, P., Babili, S.A., Avalos, J., A RALDHlike enzyme involved in Fusarium verticillioides development, Fungal Genetics and Biology (2015), doi: http:// dx.doi.org/10. 1016/j.fgb.2015.12.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A RALDH-like enzyme involved in

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“…It is tempting to speculate that BCO2, which has broader substrate specifi city, might possibly cleave stilbenoids to produce two ring aldehyde products. Other family members of carotenoid cleavage enzyme in bacteria and fungi cleave resveratrol to produce 4-hydroxy-benzaldehyde and 3,5-dihydroxy-benzaldehyde ( 45,46 ). Notably the 4 ′ hydroxyl group of resveratrol has been identifi ed as crucial for antioxidant and neuroprotective effects of stilbenoids ( 47 ).…”

Section: Discussionmentioning

confidence: 99%