The Scent of Success: Solving a Long-Standing Chemical Mystery
Have you ever wondered why cannabis, cheese, and roses have distinct scents, even though their “smell-molecules” are made from the same building blocks?
The answer lies in terpenes, a diverse group of aromatic organic compounds produced by plants, bacteria, and fungi.
These compounds are responsible for a wide range of colours and fragrances in nature. In a recent study, Professor Dan Major and his research team from the Department of Chemistry and the Institute of Nanotechnology at Bar-Ilan University solved one of the puzzles related to terpene production.
Terpenes and their slightly modified counterparts, terpenoids, play crucial roles in the survival of the organisms that produce them. They primarily serve as a defence mechanism, either repelling pests or attracting their predators. Additionally, terpenes are involved in communication, signalling the presence of food, mates, and enemies to other members of the species and their symbiotic partners. Many terpenes and terpenoids are well-known to humans as essential oils and have various medicinal properties, such as anti-inflammatory, antibiotic, mood-regulating, and even anti-cancer effects.
Terpene synthase (TPS) enzymes drive the first step in the production of terpenoids from units called isoprenoids, creating complex and intricate structures. Although all terpenes are composed of the same building blocks, they differ from one another because they are synthesized by different TPSs, which have evolved to produce distinct compounds.
Professor Major's research group focused on the active site of TPS and characterized significant differences in the chemical synthesis of terpenes for the first time. The researchers suggest that the key differences in terpene synthesis arise from the evolutionary origin of TPS—whether they come from plants, bacteria, or fungi.
To characterize these differences, the researchers employed a range of computational tools from the fields of computational biology (comparing protein sequences and identifying recurring motifs) and computational chemistry (predicting the geometry of the starting material from which terpenes are synthesized within the producing enzyme). One of the tools developed in the researchers' lab is a docking software specifically adapted for complex problems of this type. Docking software is a computerized method that has been evolving since the 1980s and is used to predict the binding "pose" of molecules and the binding energy of a small molecule (ligand) to a macromolecule such as a protein. The software uses physical equations and supercomputers to predict the spatial organization of molecules, reducing the need for expensive and tedious experimental testing of the material of interest. The tool developed in Major's lab predicts how, geometrically, the building blocks—the substrate, the starting material on which the TPS enzyme acts—will position themselves in the active site of the enzyme to be transformed into a terpene (or any other product) at the end of the process.
This research could support future attempts to produce terpenes precisely and on a large scale for a variety of medicinal and industrial applications. By understanding the mechanisms behind terpene synthesis, scientists can potentially engineer organisms to create specific terpenes with desired properties, opening up new avenues for drug discovery and development.
The study, authored by Renana Schwartz, Shani Zeev, and Professor Dan Major, was recently published in the prestigious journal Angewandte Chemie. Their findings shed light on the fascinating world of terpenes and the enzymes responsible for their production, paving the way for future advancements in this field. As we continue to unravel the mysteries of nature's building blocks, we inch closer to harnessing their potential for the benefit of humanity.