Production of trilobatin in tomato fruits: A novel biofortification approach for pharmaceutical applications
A novel biotechnology platform for producing trilobatin, a dihydrochalcone with pharmaceutical potential, directly in tomato fruits through metabolic engineering. This approach enables development of tomato varieties enriched with bioactive compounds beneficial for diabetes, Alzheimer's, cancer, obesity, and cardiovascular disease, combining health benefits with pleasant taste and low caloric value.
Overview
This solution introduces a novel approach to producing trilobatin, a dihydrochalcone representing a new class of bioactive natural products, directly in tomato fruits through genetic transformation. Dihydrochalcones offer significant potential for food and medical products, combining health-beneficial effects with pleasant sweet taste, low caloric value, and proven safety for human consumption. By engineering tomato plants to accumulate trilobatin in their fruits, this technology creates a natural source of pharmaceutical compounds for the growing market of individuals suffering from modern diseases including diabetes, Alzheimer's, cancer, obesity, and cardiovascular conditions.
Technical specifications
The platform leverages three key enzymes in the dihydrochalcone biosynthesis pathway that have been cloned and biochemically characterized:
- p-Coumaroyl-CoA double bond reductase (MdDBR) that converts p-coumaroyl-CoA into p-dihydrocoumaroyl-CoA
- Chalcone synthase (MdCHS1) that accepts p-dihydrocoumaroyl-CoA in the presence of malonyl-CoA, producing phloretin
- Phloretin-4'-O-glycosyltransferase (MdPh-4'-OGT) that glycosylates phloretin using UDP-glucose to produce trilobatin
The development approach involves constructing a multiple-gene construct containing MdDBR, MdCHS1, and MdPh-4'-OGT, followed by stable transformation of tomatoes under both constitutive 35S promoter and fruit-specific PG promoter control. Therapeutic activity evaluation will be conducted in cellular models of cancer, metabolic syndrome, neurodegenerative diseases, and inflammation.
Technology readiness level
The research is currently at an advanced proof-of-concept stage. The three key enzymes have been successfully cloned and biochemically characterized. The next phase involves synthesizing the multiple-gene construct, performing stable tomato transformation, and evaluating therapeutic activity in relevant cellular disease models. The long-term goal is to develop tomato cultivars that accumulate trilobatin as a source of pharmaceutical compounds suitable for consumption by populations affected by modern lifestyle diseases.
About Agricultural Research Organization
Israel’s Agricultural Research Organization (Volcani Center) is a national research institute that conducts fundamental and applied R&D to advance the country’s agriculture. Industry works with co‑located laboratories, pilot facilities, greenhouses, and experimental farms, and a nationwide network of research stations enables multi‑climate trials. Integration with the Ministry of Agriculture and the public extension service speeds on‑farm validation and knowledge transfer, while proximity to Israel’s agri‑tech ecosystem supports joint development. Research is supported by Israeli national funding and competitive international programs, including European framework funding. A dedicated technology transfer office manages IP, licensing, and collaboration agreements.
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