title: The oxygenase CAO-1 of Neurospora crassa is a resveratrol cleavage enzyme.
abstract: The 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 C40 carotene torulene, a key step in the synthesis of the C35 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 β-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 Cα-Cβ 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 Δcao-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 Δcao-1 colonies exhibited faster radial growth than control strains in the presence of resveratrol, suggesting a moderate toxic effect of resveratrol cleavage products.
authors.affiliation: Departamento de Genética, Universidad de Sevilla, Seville, Spain.
authors.forename: Violeta
authors.initials: V
authors.lastname: Díaz-Sánchez
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Estrada
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Limón
authors.forename: Salim
authors.initials: S
authors.lastname: Al-Babili
authors.forename: Javier
authors.initials: J
authors.lastname: Avalos
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009154:Mutation; D009492:Neurospora crassa / Q000187:drug effects / Q000201:enzymology*; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D012717:Sesquiterpenes / Q000494:pharmacology; D013013:Sorbose / Q000494:pharmacology; D013267:Stilbenes / Q000378:metabolism* / Q000494:pharmacology; D000094162:Phytoalexins
chemical_list: D012333:RNA, Messenger; D012717:Sesquiterpenes; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D010105:Oxygenases; C500451:carotenoid oxygenase; D013013:Sorbose; D000077185:Resveratrol; D000094162:Phytoalexins
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