title: Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin.
abstract: (+)-Sesamin, a furofuran class lignan, is widespread in vascular plants and represented by Sesamum spp. (+)-Sesamin has been of rapidly growing interest because of its beneficial biological effects in mammals, but its biosynthesis and physiological roles in plants remain to be clarified. It is speculated to be synthesized from (+)-pinoresinol by means of (+)-piperitol by formation of two methylenedioxy bridges mediated by two distinct Sesamum indicum cytochrome P450 (SiP450) proteins. Here, we report an SiP450, CYP81Q1, that alone catalyzes (+)-sesamin biosynthesis from (+)-pinoresinol by means of (+)-piperitol by forming two methylenedioxy bridges. The CYP81Q1 gene expression profile was temporally consistent with the accumulation pattern of (+)-sesamin during seed development. The CYP81Q1-GFP chimera protein was colocalized with an endoplasmic reticulum (ER)-targeting chimera protein, indicating that (+)-sesamin biosynthesis occurs on the ER cytoplasmic surface. Moreover, we isolated two CYP81Q1 homologs from other Sesamum spp. Sesamum radiatum CYP81Q2 showed dual (+)-piperitol/(+)-sesamin synthetic activity. CYP81Q2, as well as CYP81Q1, therefore, corresponds to a (+)-piperitol/(+)-sesamin synthase in lignan biosynthesis. In contrast, Sesamum alatum CYP81Q3 showed no activity, in accord with (+)-sesamin being deficient in S. alatum. Our findings not only provide insight into lignan biosynthesis but also unravel a unique mode of cytochrome P450 action.
authors.affiliation: Institutes for Advanced Technology, Suntory, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima, Osaka 618-8503, Japan. eiichiro.ono@suntory.co.jp
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ono
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukui
authors.forename: Namino
authors.initials: N
authors.lastname: Tomimori
authors.forename: Masako
authors.initials: M
authors.lastname: Fukuchi-Mizutani
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Honoo
authors.initials: H
authors.lastname: Satake
authors.forename: Takaharu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masumi
authors.initials: M
authors.lastname: Katsuta
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Umezawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D004149:Dioxoles; D005663:Furans / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D017705:Lignans / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D031685:Sesamum / Q000201:enzymology* / Q000235:genetics
chemical_list: D004149:Dioxoles; D005663:Furans; D017705:Lignans; D010940:Plant Proteins; D003577:Cytochrome P-450 Enzyme System; C054125:sesamin