Crop improvement for enhanced folate

Authors: Kyei-Badu, Betsy; Giovannoni, James

Submitted to: Journal of Horticultural Science and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2025
Publication Date: 8/1/2025
Citation: Kyei-Badu, B.B., Giovannoni, J.J. 2025. Crop improvement for enhanced folate. Journal of Horticultural Science and Biotechnology. 100(5):615-627. https://doi.org/10.1080/14620316.2025.2534574.
DOI: https://doi.org/10.1080/14620316.2025.2534574

Interpretive Summary: Folate is essential to human health and acquired solely through dietary intake. However, many staple crops are poor sources. Its synthesis pathway in plants is complex, compartmentalized in the cell, and highly regulated, making modification of pathway activity toward elevated folate levels challenging. The last 20 years have seen considerable effort toward folate bioengineering in crops, leading to regulatory insights that could drive optimal modification strategies. We review these prior efforts and opportunities for breeding and utilization of alternative crops to meet human folate needs. With global malnutrition still affecting over two billion people, sustainable folate enhancement strategies have the potential to improve public health outcomes, especially in regions where supplementation and industrial fortification remain limited.

Technical Abstract: Agricultural crops, including grains, tubers, vegetables and fruits, are essential to human health, economic stability, and broader food security. While breeding continues to necessarily emphasize yield and performance, in recent years, consumer food preferences have helped drive crop and especially fresh vegetable and fruit improvement. Folates are tripartite molecules, consisting of pterin, para-aminobenzoate (pABA) and glutamate moieties. The biosynthesis of folate in plants is distinctive due to its sequential and compartmentalized synthesis across the cytosol, chloroplast, and mitochondria. While single gene modifications have been less successful, combining multiple genes through gene stacking has produced synergistic enhancements in folate accumulation, as observed in both transgenic rice and tomato. These strategies can be further refined using gene-editing to reduce regulatory complexity, ensure precise modification and minimize off-target effects. Integrated omics datasets can uncover previously unknown regulatory nodes in addition to interactions between folate metabolism and related pathways that might provide novel targets for folate optimization. The long-term success of folate biofortification will depend not only on these molecular advances but also on the effective integration of genomics approaches with conventional breeding programs, facilitating the selection or modification of multiple and synergistic folate improvement traits and the targeting of multiple micronutrients simultaneously, where feasible. With global malnutrition still affecting over two billion people, sustainable folate enhancement strategies have the potential to improve public health outcomes, especially in regions where supplementation and industrial fortification remain limited.