Integrated metabolome and transcriptome analyses reveal insights into how macro-terroir affects polyphenols of Cabernet Sauvignon grapes

• The formation mechanism of grape polyphenols was evaluated in three macro- terroirs . • Low heat stress and rainfall in Ningxia favored polyphenol accumulation. • High temperatures in Xinjiang altered proportion of 3′5′-hydroxylated anthocyanins. • Genes involved in phenylpropanoid metabolism were downregulated in Hebei grapes. Understanding the plasticity of grape flavor in response to environmental factors is essential for making full use of terroir characteristics. Various studies have investigated the effect of terroir on grape polyphenols, but very few have been conducted on a macro-scale. This study selected commercial vineyards from three regions in eastern and western China (Hebei, Ningxia, Xinjiang), covering a range of 900 to 3000 km. The variation in macroclimate across these regions dominated grapevine growth, grape hormone levels, and ripening rate, which could mask the effects of soil and other factors. Low rainfall and heat stress levels in Ningxia were beneficial for accumulating delphinidin, petunidin, and malvidin-based anthocyanins, glucosylated flavonols, and phenolic acids in grapes, while high temperatures in Xinjiang increased the proportion of 3′5′hydroxylated anthocyanins. In contrast, the downregulation of genes involved in phenylpropanoid metabolism (trans-cinnamate 4-monooxygenase, 4-coumarate: CoA ligase 8, chalcone-flavonone isomerase 1, flavanone 3-hydroxylase 2, phenylalanine ammonia-lyase 1) in Hebei berries led to lower grape polyphenol levels. Most known transcription factors, such as MYBA1-A3, MYBF1, and HY5, were significantly upregulated in Ningxia grapes, correlating with the trend of increased PAL1 (phenylalanine ammonia-lyase 1) expression. Through the correlation network analysis, some new potential regulators of polyphenol biosynthesis in the macro-terroir were identified. This study provided a clear insight into terroir research and the formation mechanism of grape polyphenols in the main wine production regions of China.