Journal Article

Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates twin dietary lignans in sesame

Horikawa, Manabu, Nagano, Atsushi J., Azuma, Toshiaki, Ono, Eiichiro, Murata, Jun, Nakayasu, Masaru, Yoroizuka, Seigo, Mori, Shoko, Wakasugi, Tatsuya, Shiraishi, Akira, Mizutani, Masaharu, Yamamoto, Masayuki P., Toyonaga, Hiromi, Tera, Masayuki

2017

Overview

(+)-Sesamin, (+)-sesamolin, and (+)-sesaminol glucosides are phenylpropanoid-derived specialized metabolites called lignans, and are rich in sesame ( Sesamum indicum ) seed. Despite their renowned anti-oxidative and health-promoting properties, the biosynthesis of (+)-sesamolin and (+)-sesaminol remained largely elusive. Here we show that (+)-sesamolin deficiency in sesame is genetically associated with the deletion of four C-terminal amino acids (Del4C) in a P450 enzyme CYP92B14 that constitutes a novel clade separate from sesamin synthase CYP81Q1. Recombinant CYP92B14 converts (+)-sesamin to (+)-sesamolin and, unexpectedly, (+)-sesaminol through an oxygenation scheme designated as oxidative rearrangement of α-oxy-substituted aryl groups (ORA). Intriguingly, CYP92B14 also generates (+)-sesaminol through direct oxygenation of the aromatic ring. The activity of CYP92B14 is enhanced when co-expressed with CYP81Q1, implying functional coordination of CYP81Q1 with CYP92B14. The discovery of CYP92B14 not only uncovers the last steps in sesame lignan biosynthesis but highlights the remarkable catalytic plasticity of P450s that contributes to metabolic diversity in nature. Sesame seeds contain phenylpropanoid-derived lignans that are potentially beneficial to human health. Here, the authors clone a cytochrome P450 enzyme that is responsible for the last steps of sesame lignan biosynthesis and show that it acts through a novel oxidative rearrangement mechanism.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/449/2667 / 631/45/607/1168 / 631/92/173 / Amino acids / Aromatic compounds / Biosynthesis / Biosynthetic Pathways - genetics / Catalysis / Cytochrome P-450 Enzyme System - classification / Cytochrome P-450 Enzyme System - genetics / Cytochrome P-450 Enzyme System - metabolism / Dioxoles - chemistry / Dioxoles - metabolism / Furans - chemistry / Furans - metabolism / Glucosides / Health promotion / Humanities and Social Sciences / Humans / Lignans / Lignans - biosynthesis / Lignans - chemistry / Metabolites / Molecular Structure / multidisciplinary / Mutation / Oxidation-Reduction / Oxidative Stress / Oxygenation / Phylogeny / Plant Proteins - genetics / Plant Proteins - metabolism / Science / Science (multidisciplinary) / Sesamum - genetics / Sesamum - metabolism / Sesamum indicum