Engineering Provitamin A (Beta-carotene) Rich Tomatoes

About the Project

Background: Poor diets are a leading contributor to chronic diseases such as cardiovascular disease, certain cancers, and obesity. Social inequities further restrict access to healthy diets. The EAT-Lancet Commission has emphasized the urgent need to increase consumption of high-quality plant-based foods while reducing reliance on meat and dairy to improve both human health and environmental sustainability. Tomatoes and other fruits are excellent plant-based options due to their high nutrient density compared to starchy staples. From a planetary health perspective, plant-based foods also have significantly lower greenhouse gas emissions than animal-based foods.

Researchers at RHUL have identified an exotic allele of the carotenoid biosynthetic enzyme lycopene beta-cyclase, which converts lycopene (responsible for the red colour of ripe tomatoes) into beta-carotene, producing orange fruit. This discovery has already been commercialized by Burpee Ltd., resulting in a successful market variety. While this allele reliably confers high beta-carotene levels, the underlying mechanisms remain unclear. The HiVitA project aims to elucidate these biochemical and molecular processes. Using a population with a gradient of beta-carotene content, we will correlate biochemical measurements with gene expression, protein abundance, and enzyme activity. A multi-omics approach will explore broader metabolic contributions, and cutting-edge Programmable Transcriptional Activation technology will test whether transcriptional control drives the phenotype.

Beta-carotene offers numerous health benefits, including roles in inflammation, cellular differentiation, and immune function. Its primary importance, however, lies in its role as provitamin A, essential for human health since mammals cannot synthesize vitamin A. Vitamin A deficiency (VAD) remains widespread in low- and middle-income countries. The allele under study produces beta-carotene levels in tomato fruit two orders of magnitude higher than Golden Rice or yellow cassava, offering a powerful nutritional intervention. Beyond health benefits, this work aligns with multiple Sustainable Development Goals (SDGs), addressing malnutrition and improving food security.

Our previous collaborations with industry have demonstrated the commercial viability of this discovery, contributing to economic growth. HiVitA will build on this success by developing new strategies for market translation, fostering technological innovation, and providing advanced skills training with entrepreneurial applications. The project will generate valuable data to inform policy and benefit the scientific community, ensuring impact across all stakeholders in the value chain.

Aims and objectives: This project aims to characterise the Tomato S. galapagense lycopene beta-cyclase (Cyc-B) as a key genetic resource for conferring high beta-carotene (provitamin A) content in ripe tomato fruit. The Objectives include

1. Leverage the natural variation within the S. galapagense RIL population to establish correlations between the presence, transcription, and activity of Cyc-B and beta-carotene content. Comparisons will be made with existing transgenic lines that produce high beta-carotene.
2. Conduct detailed characterisation of the carotenoid biosynthetic pathway and perform systems-level analysis to identify direct and indirect metabolic responses associated with altered beta-carotene levels.
3. Apply programmable transcriptional activation technology to determine whether targeted transcriptional activation of Cyc-B, in a background-independent manner, can achieve high beta-carotene accumulation in ripe tomato fruit.
4. Use in vitro digestion models to show superior Absorption, Distribution, Metabolism and Excretion (ADME) parameters for beta carotene.

Training: This project will provide the candidate with generic training in Biochemistry and Molecular Biology. Specifically, metabolite analysis, enzyme assays. The molecular techniques will include vector construction, modern gene editing approaches transcripts analysis and transgenesis.

Environment: The laboratory is fully equipped with advanced analytical and plant growth facilities to support the proposed research. Dedicated instrumentation includes GC-MS (×3), GC-FID, HPLC-PDA (×2), HPLC-PDA with radiodetector, UPLC-PDA, and real-time PCR systems, including digital droplet PCR (Bio-Rad QX200). Plant growth resources comprise 800 m² of glasshouses, a controlled tissue culture room for transformations, growth chambers, and 600 m² of polytunnels.

Our state-of-the-art analytical suite features complementary mass spectrometry platforms:

• LC-QTOF-MS/MS (Agilent IM-6560 and iFunnel 6550) for metabolomics and proteomics
• LC-QQQ-MS (Agilent 6470) for precise quantitative analysis

Protein purification is supported by multiple ultracentrifuges and a Cytiva ÄKTA Pure system with a full range of columns. Imaging capabilities include Scanning and Transmission Electron Microscopes (SEM/TEM) and confocal laser scanning microscopes for 3D live-cell imaging.

The research environment is collaborative, diverse, and strongly supportive of career development. The Concordat to Support the Career Development of Researchers (www.researchdevelopmentconcordat.ac.uk) is fully implemented, and the investigators actively promote progression opportunities for all team members.

Funding Notes

Supervisor has applied for funding and is awaiting outcomes.

If the candidates have the correct qualifications and/or access to own funding or partial funding , either from their home country or own finances, your application can be considered.