Some raw materials used in perfume are obtained by further processing molecules made by plants. One such starting molecule is sclareol, found in clary sage. It is used as a raw material for manufacturing fragrance ingredients that substitute for ambergris.
Why, then, did clary sage acquire the ability to make this molecule? A study published in May 2026 explored its evolutionary history by examining the plant’s genetic information and enzyme activity. The clues were copies created by gene duplication and changes in just a small part of an enzyme.
Tracing a molecule before it becomes a fragrance ingredient
The subject here is how sclareol is made inside the plant. The scent of fragrance ingredients subsequently produced from it must be distinguished from the odor of sclareol itself. This study did not assess the intensity or impression of its smell to people.
In plant cells, proteins called enzymes drive chemical reactions. In the pathway that produces sclareol, one enzyme first converts the starting material GGPP into an intermediate called LPP. Another enzyme then acts to produce sclareol. An intermediate is a substance formed on the way to the final molecule.
The enzymes responsible for this two-step reaction were already known from earlier research. The question this time was how that ability arose during evolution.
A gene copy acquires a new role
The team examined the clary sage genome in detail and compared it with those of related Salvia plants and other species. A genome is an organism’s complete set of genetic information. By studying the arrangement and similarity of genes, researchers can infer which genes were inherited from a common ancestor and where their numbers increased.
They focused on the gene for the enzyme that produces LPP. The comparison suggested that a gene for an enzyme producing another intermediate, CPP, had duplicated and subsequently changed function. Duplication creates another similar gene. As changes accumulate in a copy, it may acquire a role different from that of the original gene.
This acquisition of a new function by a duplicated gene is called neofunctionalization. In this study, the researchers not only compared genetic information across plants but also produced the enzymes themselves and tested their activity.
What happened when six positions in an enzyme were changed?
Enzymes consist of building blocks called amino acids, linked together and folded into a three-dimensional structure. Part of that structure accommodates the molecule that will react. Changes to the shape or properties of this site can alter which substance is produced from the same starting material.
The researchers examined differences between the two enzymes using known protein structures and structural predictions. They then replaced amino acids at six positions in the CPP-producing enzyme with those found in the LPP-producing enzyme.
The enzymes were produced in Escherichia coli, purified, and allowed to react outside the plant. After processing the products for analysis, the team examined them by gas chromatography–mass spectrometry, a method that separates mixed components and identifies the substances produced.
The substituted enzyme acquired the ability to make LPP in addition to its original product, CPP. The important point is that, beyond genetic similarity, an experiment changing specific amino acids demonstrated a change in the substances produced.
The reverse substitutions did not have the corresponding effect. Restoring the equivalent positions in the LPP-producing enzyme did not restore CPP-producing activity. Although the six differences were implicated in the new function, changes elsewhere in the enzyme are also thought to matter. This experiment did not recreate every change that occurred during evolution.
Not just the ability to make it, but where it is made
Even when a plant has the necessary enzymes, production depends on where their genes are active. Sclareol accumulates in small hair-like structures called glandular trichomes in floral tissues.
The study examined tissues including flowers, leaves, and roots, confirming high expression of genes involved in sclareol synthesis in glandular trichomes. It also showed that related genes cluster near one another on a chromosome and form a group active in trichomes and another group involved in producing different substances in roots.
The researchers also analyzed how DNA is packaged with surrounding proteins and how accessible it is for reading. Regions involved in reading trichome-active genes were more accessible in trichomes. Both changes in enzyme activity and regulation that produces those enzymes in the right place are thought to support sclareol production.
Conclusion
Clary sage is thought to have acquired the ability to produce sclareol as gene copies changed and the enzymes they encoded gained new functions. Supporting that inference is the experiment in which substitutions at six amino acid positions enabled an enzyme to make an intermediate leading to sclareol alongside its original product.
Regulation that produces the necessary enzymes in floral tissues is also thought to support sclareol production. Six changes alone do not explain the entire evolutionary process. The significance of this study lies in examining how a fragrance raw material arises from both the substances an enzyme can make and where in the plant that enzyme is put to work.
Original paper
Fei Dong, Marion Verdenaud, Gabriele Adam et al.
Neofunctionalization underlies the evolutionary origin of sclareol biosynthesis in the mint family
Nature Communications 17, 6745 (2026).
First published: May 22, 2026. Publisher’s Version of Record date: July 21, 2026.
DOI: https://doi.org/10.1038/s41467-026-73637-5
Full text: https://www.nature.com/articles/s41467-026-73637-5
Original paper license: CC BY 4.0
https://creativecommons.org/licenses/by/4.0/
This article was independently written as a Japanese explanation of the original paper. It does not translate the original paper or reproduce its figures or tables.
The coauthors include two researchers affiliated with fragrance company Symrise. The authors declare no competing interests.
