Mechanism of Phloretin Accumulation in <i>Malus hupehensis</i> Grown at High Altitudes: Evidence from Quantitative 4D Proteomics

Phloretin is a natural dihydrochalcone (DHC) that exhibits various pharmacological and therapeutic activities. <i>Malus hupehensis</i> Rehd. (<i>M. hupehensis</i>) is widely planted in the middle of China and its leaves contain an extremely high content of phloridzin, a glycosylated derivative of phloretin. In the present study, we observed a significant increase in phloretin content in the leaves of <i>M. hupehensis</i> planted at high altitudes. To investigate the mechanisms of phloretin accumulation, we explored changes in the proteome profiles of <i>M. hupehensis</i> plants grown at various altitudes. The results showed that at high altitudes, photosynthesis- and DHC biosynthesis-related proteins were downregulated and upregulated, respectively, leading to reduced chlorophyll content and DHC accumulation in the leaves. Moreover, we identified a novel phloridzin-catalyzing glucosidase whose expression level was significantly increased in high-altitude-cultivated plants. This work provided a better understanding of the mechanism of phloretin accumulation and effective and economic strategies for phloretin production.