In brief

Alterations in the amino acid sequence of fungal linalool synthase influence the enzyme’s terpenoid end-product, offering a strategic blueprint for bioengineering more targeted and efficient terpene synthases for use in a wide range of industrial applications.

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Manufacturing nature’s sweet smells

25 Jan 2024

In a breakthrough study, researchers identify how an enzyme found in fungi produces a natural chemical commonly used in cosmetics, fragrances and medicines.

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).

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T, R., Sharma, D., Lin, F., Choong, Y.K., Lim, C., et al. Structural understanding of fungal terpene synthases for the formation of linear or cyclic terpene products. ACS Catalysis 13 (7), 4949–4959 (2023). | article

Zhang, C., Chen, X., Lee, R.T.C., T, R., Maurer-Stroh, S., et al. Bioinformatics-aided identification, characterization and applications of mushroom linalool synthases. Communications Biology 4 (223), (2021). | article

About the Researchers

Congqiang Zhang (Simon) received his undergraduate and master training in chemical engineering at Tianjin University, China. He then continued with his PhD training in Chemical and Pharmaceutical Engineering in a joint programme between National University of Singapore and Massachusetts Institute of Technology. He is now a Principal Investigator at the Singapore Institute of Food and Biotechnology Innovation (SIFBI) leading a team working on multiple academic and industrial projects. His expertise is in metabolic engineering, synthetic biology, enzyme engineering, discovery and biosynthesis of natural products and industrial biotechnology. He has co-authored over 30 papers and has 10 international patents. He served as an associate editor for two peer-reviewed journals, Advanced Biotechnology and Frontiers in Bioengineering and Biotechnology; and is the secretary for the BioEnergy Society of Singapore.
Rehka T. obtained her bachelor's degree in Bioengineering from Nanyang Technological University in July 2016. From Mar 2017 to Aug 2018, she worked at Singapore-MIT Alliance for Research and Technology (SMART) as a Laboratory Technologist in the Infectious Diseases department where she focused extensively on the proteomics of bacterial infection. She then joined A*STAR and was with the Biotransformation Innovation Platform (BIP) before moving to the Singapore Institute of Food and Biotechnology Innovation (SIFBI). Her focus has been mainly on enzyme engineering of terpene synthases for the production of valuable terpenoids. Last year, she represented SIFBI and was one of three participants to win the best poster award at Bioflavour 2022, an event organised by Dechema and held in Frankfurt, Germany. She has published six papers in journals such as Nature Communications and ACS publications.

This article was made for A*STAR Research by Wildtype Media Group