AUTHOR=Kenea Fikru Tamiru , He Nan , Lu Xuqiang , Luo Xiaowen , Zhu Hongju , Liu Wenge TITLE=Watermelon fruit metabolome gene discovery and its application in breeding: a review JOURNAL=Frontiers in Plant Science VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2025.1687406 DOI=10.3389/fpls.2025.1687406 ISSN=1664-462X ABSTRACT=Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is a globally important vegetable crop valued for its taste, hydration, and nutritional benefits. Recent advances in multi-omics technologies have accelerated the identification of genes controlling key fruit metabolites that impact fruit quality traits such as sweetness, bitterness, sourness, aroma, texture, and color. This review synthesizes the current knowledge on watermelon genes regulating and transporting fruit metabolites, including sugars, cucurbitacin, organic acids, carotenoids, amino acids, flavonoids, and volatile organic compounds that impact fruit quality. Both forward and reverse genetics approaches, coupled with high-throughput phenotyping, have been instrumental in these gene discoveries. Breeding applications, including marker-assisted selection (MAS) and genomic selection (GS), are highlighted, emphasizing their potential to enhance fruit metabolites that improve fruit quality and nutritional value. Emerging technologies, such as CRISPR/Cas9-mediated gene editing, have been employed to uncover and validate CIVST1, PSY1, and PEPCK genes, enabling precision breeding for improved fruit metabolite profile. However, challenges persist due to the environmental sensitivity and polygenic nature of fruit metabolites, the narrow genetic base, and the limited adoption of molecular breeding methods like CRISPR/Cas9. Future directions emphasize leveraging wild germplasm, integrating AI-driven phenotyping, and applying precision breeding strategies. These approaches will enable the development of next-generation watermelon cultivars with improved multi-trait quality and nutritional profiles to meet evolving market demands.