Figure 1: A schematic diagram depicting the catalysis of the biosynthesis of a terpenoid by the two domains (green and cyan structures) of a bacterial terpene cyclase. © Reproduced from Ref. 1 and licensed under CC BY 3.0 © 2026 K. Fujiyama et al.
The molecular structure of an enzyme from a marine bacterium with potential industrial uses has been determined by RIKEN researchers1. The insights they have gained could help make a range of useful compounds through genetic modification.
The class of natural compounds known as terpenoids is nothing if not versatile, being used in a wide assortment of products from perfumes and insect repellents to pesticides and drugs. More than 100,000 terpenoids have been identified so far. They are produced by an impressive range of organisms spanning animals, plants, fungi, bacteria and viruses.
Recently, marine organisms such as corals, sponges and marine bacteria have been found to produce terpenoids with complex structures that show promise for fighting infectious diseases.
The diversity of terpenoids stems from the enzymes that organisms use to synthesize them, which are called terpene cyclases. These enzymes are frequently used in industry.
"Pharmaceutical, perfume and food companies often use terpene cyclases to produce drugs, fragrances and flavors," notes Shunji Takahashi of the RIKEN Center for Sustainable Resource Science, who has long studied terpenoids, including the biosynthesis of compounds in fungi in collaboration with a Japanese soy-sauce manufacturer.
However, until now, no one had determined the structures of terpene cyclases in marine organisms.
Now, Takahashi and his co-workers have gained valuable structural insights into a terpene cyclase from a marine bacterium that lives in sponges. They did this by preparing crystal samples of the terpene cyclase and performing X-ray diffraction on them.
"Its substrate-bound structure and reactions are really unique," says Takahashi. "This is the first time they have been determined."
Takahashi and his team found that the two main components that make up the terpene cyclase play different roles in catalyzing the biosynthesis of terpenoids.
Most sesquiterpene cyclases initiate catalysis by removing a phosphate group to generate a carbocation. In contrast, this enzyme forms the carbocation through protonation of the substrate. The second domain, which is only found in terpene cyclases of some marine species, catalyzes a reaction that removes a phosphate group.
"We were surprised when we discovered this two-part mechanism in the same molecule," says Takahashi. "It enhances the efficiency of the enzymatic reaction."
To compare the structure the team had found with related fungal enzymes whose crystal structures remain unresolved, the team employed AlphaFold2, an AI platform that predicts 3D protein structures from amino-acid sequences.
The team now hopes to develop new compounds with potential industrial applications using the discovered scaffold. They also want to explore the evolutionary aspects of terpene cyclases.
Shunji Takahashi (second row; third from left) and his team have gained insights into the structure of a bacterial terpene cyclase fused with haloacid dehalogenase-like phosphatase. © 2026 RIKEN
