title: Cyclofarnesoids and methylhexanoids produced from β-carotene in Phycomyces blakesleeanus.
abstract: The oxidative cleavage of β-carotene in the Mucorales produces three fragments of 18, 15, and 7 carbons, respective heads of three families of apocarotenoids: the methylhexanoids, the trisporoids, and the cyclofarnesoids (named after their 1,6-cyclofarnesane skeleton). The apocarotenoids are easily recognized because they are absent in white mutants unable to produce β-carotene. In cultures of Phycomyces blakesleeanus we detected thirty-two apocarotenoids by LC, UV absorbance, and MS. With additional IR and NMR we identified two methylhexanoids and the eight most abundant cyclofarnesoids. Four of them were previously-unknown natural compounds, including 4-dihydrocyclofarnesine S, the most abundant cyclofarnesoid in young cultures. We arranged the apocarotenoids of the Mucorales in a scheme that helps classifying and naming them and suggests possible metabolites and biosynthetic pathways. We propose specific biosynthetic pathways for cyclofarnesoids and methylhexanoids based on structural comparisons, the time course of appearance of individual compounds, and the bioconversion of β-apo-12-carotenol, an early precursor, to three more oxygenated cyclofarnesoids by the white mutants. Some of the reactions occur spontaneously in the increasingly acidic culture media. Mating increased the contents of methylhexanoids and cyclofarnesoids by ca. threefold in young cultures and ca. twelvefold in old ones (five days); cyclofarnesine S, the most abundant cyclofarnesoid in old cultures, increased over one hundredfold. We found no differences between the sexes and no activity as sexual pheromones, but we suggest that methylhexanoids and cyclofarnesoids could mediate species-specific physiology and behavior.
authors: Departamento de Genética, Universidad de Sevilla, Apartado 1095, E-41080 Sevilla, Spain. Electronic address: eugenalc@gmail.com.
authors: Eugenio
authors: E
authors: Alcalde
authors: Departamento de Genética, Universidad de Sevilla, Apartado 1095, E-41080 Sevilla, Spain. Electronic address: hurmedina@gmail.com.
authors: Humberto R
authors: HR
authors: Medina
authors: Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, Fuente Nueva s/n, E-18071 Granada, Spain. Electronic address: mmar@ugr.es.
authors: M Mar
authors: MM
authors: Herrador
authors: Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, Fuente Nueva s/n, E-18071 Granada, Spain. Electronic address: afbarre@ugr.es.
authors: Alejandro F
authors: AF
authors: Barrero
authors: Departamento de Genética, Universidad de Sevilla, Apartado 1095, E-41080 Sevilla, Spain. Electronic address: eco@us.es.
authors: Enrique
authors: E
authors: Cerdá-Olmedo
mesh_terms: D053898:Biosynthetic Pathways; D002338:Carotenoids / Q000737:chemistry* / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D009090:Mucorales / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010800:Phycomyces / Q000737:chemistry*; D012724:Sex Attractants / Q000378:metabolism; D019207:beta Carotene / Q000737:chemistry*
chemical_list: D003470:Culture Media; D012724:Sex Attractants; D019207:beta Carotene; D002338:Carotenoids
keywords: Apocarotenoids; Bioconversion; Cyclofarnesoids; Methylhexanoids; Mucorales; Phycomyces blakesleeanus; Phycomycetaceae; β-Carotene