Cleavage of resveratrol in fungi: Characterization of the enzyme Rco1 from Ustilago maydis

Brefort, Thomas; Scherzinger, Daniel; Limón, M. Carmen; Estrada, Alejandro F.; Trautmann, Danika; Mengel, Carina; Ávalos, Javier; Al‐Babili, Salim

doi:10.1016/j.fgb.2010.10.009

Cited by 32 publications

(42 citation statements)

References 63 publications

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“…Retinal formation may be particularly relevant in U. maydis, which contains three presumptive rhodopsin-encoding genes. Unexpectedly, the second CCO enzyme, Rco1, showed no activity on carotenoid substrates but cleaved resveratrol (36). Similar resveratrol-cleaving enzymes were identified in the fungi Aspergillus fumigatus, Chaetomium globosum, and Botryotinia fuckeliana (36).…”

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confidence: 66%

“…Incubation of the recombinant CAO-1 protein in vitro with resveratrol resulted in the formation of two products (Fig. 3B, insets a and b) with elution times and UV spectrum maximal absorptions identical to those of 3,4-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde, the compounds resulting from the resveratrol cleavage activity by U. maydis Rco1 (36). Liquid chromatography-mass spectrometry (LC-MS) analyses (data not shown) confirmed the identity of both products and proved the oxidative cleavage at the interphenyl double bond of resveratrol (Fig.…”

Section: Cao-1 Is Not Associated With Carotenoid Metabolismmentioning

confidence: 98%

“…Unexpectedly, the second CCO enzyme, Rco1, showed no activity on carotenoid substrates but cleaved resveratrol (36). Similar resveratrol-cleaving enzymes were identified in the fungi Aspergillus fumigatus, Chaetomium globosum, and Botryotinia fuckeliana (36). The biological relevance for resveratrol-cleaving enzymes in these species remains to be elucidated.…”

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confidence: 88%

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

et al. 2013

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bThe genome of the ascomycete Neurospora crassa encodes CAO-1 and CAO-2, two members of the carotenoid cleavage oxygenase family that target double bonds in different substrates. Previous studies demonstrated the role of CAO-2 in cleaving the C 40 carotene torulene, a key step in the synthesis of the C 35 apocarotenoid pigment neurosporaxanthin. In this work, we investigated the activity of CAO-1, assuming that it may provide retinal, the chromophore of the NOP-1 rhodopsin, by cleaving ␤-carotene.For this purpose, we tested CAO-1 activity with carotenoid substrates that were, however, not converted. In contrast and consistent with its sequence similarity to family members that act on stilbenes, CAO-1 cleaved the interphenyl C␣-C␤ double bond of resveratrol and its derivative piceatannol. CAO-1 did not convert five other similar stilbenes, indicating a requirement for a minimal number of unmodified hydroxyl groups in the stilbene background. Confirming its biological function in converting stilbenes, adding resveratrol led to a pronounced increase in cao-1 mRNA levels, while light, a key regulator of carotenoid metabolism, did not alter them. Targeted ⌬cao-1 mutants were not impaired by the presence of resveratrol, a phytoalexin active against different fungi, which did not significantly affect the growth and development of wild-type Neurospora. However, under partial sorbose toxicity, the ⌬cao-1 colonies exhibited faster radial growth than control strains in the presence of resveratrol, suggesting a moderate toxic effect of resveratrol cleavage products.

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Section: Cao-1 Is Not Associated With Carotenoid Metabolismmentioning

confidence: 98%

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

et al. 2013

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“…There are several other mechanisms by which the ternary complex of Fig. 4, step A might proceed to catalysis, including dioxetane, epoxide, or Criegee rearrangements to yield aldehyde products (5).…”

Section: Resultsmentioning

confidence: 99%

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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“…It seems likely that other stilbenoids may serve as ring precursors of Q. For example, processing of piceatannol ( trans-3,5,3 ′ 4 ′ -tetrahydroxystilbene) by a fungal carotenoid cleavage oxidase family member ( 48 ), generates 3,4-dihydroxybenzaldehyde, a ring precursor that could potentially bypass the Coq6 hydroxylase step of Q biosynthesis upon Coq2-prenylation ( 49 ).…”

Section: Discussionmentioning

confidence: 99%