New Research Unlocks Triterpene Production in Horticultural Trees

Plants produce over 20,000 unique triterpenes, which possess impressive medicinal properties, including anti-inflammatory, anticancer, and antidiabetic effects. A new review published on October 8, 2024, by scientists at the National Institute of Pharmaceutical Education and Research addresses the challenges involved in harnessing these compounds from horticultural trees. Traditionally, extracting triterpenes from plants or synthesizing them chemically has proven to be time-consuming, expensive, and environmentally unsustainable.

The structural complexity of triterpenes, characterized by multiple stereocenters and unique modifications, complicates their chemical synthesis. Furthermore, many enzymes involved in triterpene biosynthesis remain unidentified, particularly in trees cultivated for fruit, nuts, and ornamental purposes. These gaps limit the potential to fully exploit triterpenes for human health and industry.

Transformative Approaches to Triterpene Research

The review highlights how advancements in synthetic biology, multi-omics, and computational tools are reshaping our understanding of triterpene biosynthesis. The researchers demonstrate how these methodologies can identify critical enzymes, facilitate pathway reconstruction in non-native hosts, and employ design-build-test-learn (DBTL) frameworks to promote the sustainable production of these valuable natural products.

Triterpenes originate from the precursor 2,3-oxidosqualene, which is transformed by enzymes known as oxidosqualene cyclases (OSCs). Subsequent modifications are carried out by cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and acyltransferases (ATs). This intricate process contributes to the expansive chemical diversity of triterpenes and underpins their broad pharmacological applications.

Recent findings from plants such as Bauhinia forficata, Lagerstroemia speciosa, and even common fruits like apples and olives have revealed significant insights. These studies have identified novel enzymes, including CYP716A259 and BfOSC3. For instance, engineered yeast strains have successfully produced high levels of morolic acid, while tobacco plants have been utilized to reconstruct the complex 20-step biosynthesis of the vaccine adjuvant QS-21.

Building a Sustainable Future

The review emphasizes the importance of using the DBTL cycle as a standard operational model. This approach integrates computational modeling, genome editing, metabolomics, and artificial intelligence to optimize the production of triterpenes. Such frameworks are crucial in addressing challenges like feedback inhibition, limited expression of biosynthetic gene clusters, and scalability issues.

Dr. Sandeep Dinday, the lead author of the study, stated, “The structural diversity of triterpenes offers enormous promise for food, medicine, and sustainable industries, yet horticultural trees remain a largely untapped resource.” By synthesizing multi-omics with synthetic biology and computational tools, researchers aim to accelerate the discovery of key biosynthetic enzymes and reconstruct pathways outside their natural environments. This work not only enhances the efficient production of known bioactive compounds but also paves the way for creating novel triterpenes with unique therapeutic or industrial applications.

The advancements in understanding triterpene biosynthetic pathways carry significant implications for various industries. Efficient bioengineering could lead to the sustainable production of valuable compounds such as ursolic acid, morolic acid, and QS-21 at an industrial scale, reducing reliance on environmentally damaging plant extraction methods. These compounds can serve as vital ingredients in pharmaceuticals, functional foods, and crop protection products.

The DBTL framework also serves as a model for applying synthetic biology to other natural product classes, from alkaloids to flavonoids. By transforming horticultural trees into effective systems for elucidating these pathways, researchers are laying the foundation for greener biomanufacturing solutions that can meet the increasing global demand for natural products.

The full review can be accessed in the journal Horticulture Research, which is recognized as an open-access leader in the horticultural field, ranked number one in its category according to the Journal Citation Reports from Clarivate in 2023.