Alongside visual cues like bright colours, plants send sweet-smelling signals to keep their ‘friends’ close—scented organic chemicals called terpenoids attract pollinators such as bees and butterflies. These fragrant molecules are also used extensively in a range of commercial processes from drug development and food flavourings to cosmetics and perfumery.
Congqiang Zhang, a Principal Investigator at A*STAR’s Singapore Institute of Food and Biotechnology Innovation (SIFBI), said that manufacturing terpenoids requires the use of terpene synthases (TPSes), elusive enzymes known to produce the terpene scaffolds that can be further diversified to a catalogue of around 200,000 different terpenoids.
“The products of tens of thousands of TPSes are still unknown, particularly the fungal ones,” explained Zhang, adding that this is largely because characterising terpenoids structurally is time-consuming and expensive, a process that requires specialised analytical technologies.
However, overcoming these barriers hold enormous commercial value. “With a deep mechanistic understanding of TPSes, we can eventually predict their main products without extensive experiments, enabling us to engineer next-generation, high-efficiency TPSes for specific terpenoid products,” noted Zhang.
In collaboration with researchers from CNRS@CREATE and the National University of Singapore, Zhang’s team investigated the crystal structure of a TPS called fungal linalool synthase, which is known to produce linalool (a natural terpenoid with a lavender fragrance and strong antibacterial properties routinely used in shampoos and soaps). The team performed a battery of tests to identify key regions and amino acids that influenced the enzyme’s specificity.
They zeroed in on a specific amino acid called Tyr299 which dictated whether fungal linalool synthase produced linear or ring-shaped cyclic terpenoids. They discovered that altering Tyr299 resulted in the TPS shifting its production of linalool to longer, chain-like terpenoid products.
Zhang said that this is the first report of a crystal structure for a fungal monoterpene synthase, which adds to a very limited set of fully characterised TPSes of microbial origin. “Therefore, this study provides an important template to model other uncharacterised microbial terpene synthases in nature,” commented Zhang.
These fresh insights on how the structural features of TPSes govern product specificity open up possibilities for creating customised enzymes with targeted functions for numerous natural product synthesis applications. According to Zhang, the team is optimising other aspects of linalool bioproduction and have filed patents to commercialise the use of their innovative TPS technology.
The A*STAR researchers contributing to this research are from the Singapore Institute of Food and Biotechnology Innovation (SIFBI) and the Bioinformatics Institute (BII).
