Plants produce more than 20,000 distinct triterpenes, often with potent anti-inflammatory, anticancer, or antidiabetic properties. Traditionally, these molecules were extracted directly from plants or synthesized chemically, approaches that are time-consuming, costly, and unsustainable at scale. Their structural complexity, marked by multiple stereocenters and specialized decorations, poses additional challenges for chemical synthesis. Moreover, many triterpene biosynthetic enzymes remain unidentified, particularly in horticultural trees used for fruit, nut, and ornamental production. These gaps hinder our ability to fully exploit triterpenes for human benefit. Based on these challenges, there is a pressing need to conduct in-depth research on triterpene biosynthetic pathways in horticultural trees.
A new review article was published (DOI: 10.1093/hr/uhae254) in Horticulture Research on October 8, 2024. Conducted by scientists at the National Institute of Pharmaceutical Education and Research, the review highlights how synthetic biology, multi-omics, and computational tools are transforming our understanding of triterpene biosynthesis. The study outlines how these approaches reveal key enzymes, enable pathway reconstruction in heterologous hosts, and propose design-build-test-learn frameworks to advance sustainable production of these high-value natural products.
The review emphasizes that triterpenes are generated from the precursor 2,3-oxidosqualene via oxidosqualene cyclases (OSCs), before undergoing modifications by cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and acyltransferases (ATs). These steps create an immense chemical diversity that underpins triterpenes’ broad pharmacological activities. Recent discoveries in species such as Bauhinia forficata, Lagerstroemia speciosa, apple, olive, and Quillaja saponaria illustrate how multi-omics and pathway reconstruction strategies have identified novel enzymes like CYP716A259 and BfOSC3. For example, engineered yeast strains have produced high titers of morolic acid, while tobacco plants were used to reconstitute the 20-step biosynthesis of vaccine adjuvant QS-21. Importantly, the review highlights the use of design-build-test-learn (DBTL) cycles as a standard workflow, integrating computational modeling, genome editing, metabolomics, and artificial intelligence to optimize production. Such frameworks help overcome challenges like feedback inhibition, low expression of biosynthetic clusters, and scalability issues. Collectively, these efforts provide a roadmap for refactoring complex triterpene pathways in heterologous hosts, bridging the gap between basic discovery and industrial application.
“The structural diversity of triterpenes offers enormous promise for food, medicine, and sustainable industries, yet horticultural trees remain a largely untapped resource,” said lead author Dr. Sandeep Dinday. “By combining multi-omics with synthetic biology and computational tools, we can accelerate the discovery of key biosynthetic enzymes such as OSCs and CYP716s, and reconstruct pathways outside of their native hosts. This opens opportunities not only for producing known bioactive compounds more efficiently but also for creating new-to-nature triterpenes with unique therapeutic or industrial properties.”
Advancing the understanding of triterpene biosynthetic pathways has far-reaching implications. Efficient bioengineering could enable sustainable production of valuable triterpenes such as ursolic acid, morolic acid, and QS-21 at industrial scale, reducing reliance on environmentally costly plant extraction. These molecules can serve as active ingredients in pharmaceuticals, functional foods, and crop protection products. The DBTL framework also provides a blueprint for adapting synthetic biology to other natural product classes, from alkaloids to flavonoids. By turning horticultural trees into models for pathway elucidation, researchers are laying the groundwork for greener biomanufacturing solutions that meet growing global demands.
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References
DOI
10.1093/hr/uhae254
Original Source URL
https://doi.org/10.1093/hr/uhae254
About Horticulture Research
Horticulture Research is an open access journal of Nanjing Agricultural University and ranked number one in the Horticulture category of the Journal Citation Reports ™ from Clarivate, 2023. The journal is committed to publishing original research articles, reviews, perspectives, comments, correspondence articles and letters to the editor related to all major horticultural plants and disciplines, including biotechnology, breeding, cellular and molecular biology, evolution, genetics, inter-species interactions, physiology, and the origination and domestication of crops.