Unraveling the Lignan Metabolic Control Mechanism Across Developmental Stages

## Overview

A joint research group led by the Suntory Institute for Bioorganic Research (SUNBOR), including Toyama University, Tohoku University, the National Institute for Basic Biology, and Suntory Global Innovation Center Ltd., has clarified how sesame seeds extensively convert sesamin, a major lignan component, into other compounds during germination.

The research group discovered a new group of cytochrome P450 (CYP) enzymes, 'CYP706V12–V14,' that act specifically during germination. They revealed that these enzymes, in coordination with glycosyltransferase (UGT) groups, gradually convert fat-soluble sesamin lignans into water-soluble lignan glycosides.

Furthermore, it was revealed that sesame seeds flexibly switch their metabolic networks according to their developmental stage by using different enzyme groups during the seed maturation period and the germination period. These findings demonstrate how plants dynamically reconfigure their metabolic systems according to their developmental stage. This provides new insights into the evolution of plant-specific metabolism and is expected to be applied to the development of sesame varieties with high contents of functional components.

This research was published in the 'Proceedings of the National Academy of Sciences of the United States of America (PNAS).'

[Key Points of this Research]

- Discovered the new sesamin oxidase group 'CYP706V12–V14' that works during sesame germination.
- Clarified the mechanism by which CYP enzyme groups and glycosyltransferase (UGT) groups coordinate to form water-soluble lignan glycosides.
- Discovered that metabolic networks are dynamically reconfigured by using different enzyme groups during maturation and germination.

## Background

Sesame seeds are rich in fat-soluble lignans such as sesamin. Previously, the research group was the first in the world to identify the sesamin oxidase 'CYP92B14' that works during seed maturation, clarifying lignan biosynthesis in mature seeds.

However, although it was known that these fat-soluble lignans rapidly decrease and are converted into water-soluble glycosides during germination, the enzyme groups and regulatory mechanisms responsible for this metabolic conversion were unclear.

## Results

In this study, by combining metabolite analysis, gene expression analysis, and enzyme function analysis, the research group discovered new sesamin oxidase groups 'CYP706V12–V14' and glycosyltransferase (UGT) groups that are specifically expressed during sesame germination. It became clear that the CYP706V enzyme group forms a metabolic network different from the known enzyme 'CYP92B14' that functions in mature seeds, and that it is responsible for the unique metabolism of the germination period by oxidizing sesamin.

Furthermore, it was revealed that the UGT group forms various water-soluble lignan glycosides by efficiently coordinating with the oxidation reaction by the CYP enzyme group and gradually adding sugars.

Also, when examining a sesame line that does not accumulate a specific component (sesaminol glycoside) during the maturation period, it was found that the enzyme 'CYP706V12' does not function. From this, it was understood that 'CYP706V12' plays an important role not only during the germination period but also during the maturation period. This showed that sesame flexibly reconfigures its metabolic network by using different combinations of CYP and UGT enzymes according to the developmental stage. These results show that plant-specific metabolism is not fixed, but dynamically reorganized according to the developmental stage.

## Future Prospects

These findings provide new perspectives on the evolution of plant-specific metabolism and are expected to be applied to the development of sesame varieties with high contents of functional components.