Siraitia grosvenorii fruit is a traditional ingredient in Chinese tea beverages with medicinal values. Postharvest ripening of S. grosvenorii fruit involves the alteration of sweetness and the accumulation of various metabolites. This study systematically investigated the dynamic changes in physiological properties, metabolomic profiles, and gene expression patterns during postharvest ripening of S. grosvenorii fruits across four stages (P0, P3, P7, and P14). Physiological analysis revealed that prolonged ripening significantly increased moisture loss rate, soluble solid content, relative conductivity, and pericarp color change, while respiratory rate remained stable. Metabolomic profiling identified 3066 metabolites, with amino acids and their derivatives as the most abundant class. Differential accumulation analysis demonstrated that the transitions from P3-to-P7 and P7-to-P14 were crucial phases in the postharvest ripening process, characterized by significant enrichment in amino acid metabolism, aminoacyl-tRNA biosynthesis, and secondary metabolite biosynthesis pathways. Notably, the accumulation of sweet mogrosides (11-oxomogroside V and mogroside V) peaked at the late stage (P14), whereas less-sweet variants (mogroside III and IV) declined progressively. Weighted gene co-expression network analysis identified the MEturquoise module as positively correlated with desirable mogrosides and fruit quality traits. The qPCR validation revealed stage-specific upregulation of key biosynthesis genes, with SgUGT85–269–4 peaking at P3 and SgUGT94–289–3 showing highest expression at P7. These findings demonstrate that controlled postharvest ripening (up to 14 days) is essential for maximizing mogroside sweetness and fruit quality, providing a scientific basis for optimizing processing schedules in S. grosvenorii fruits production. The identified metabolic modules and gene targets offer valuable resources for future genetic and agronomic strategies to enhance mogroside yields.
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