摘要Among plant metabolites,phenolamides,which are conjugates of hydroxycinnamic acid derivatives and polyamines,play important roles in plant adaptation to abiotic and biotic stresses.However,the molecular mechanisms underlying phenolamide metabolism and regulation as well as the effects of domestication and breeding on phenolamide diversity in tomato remain largely unclear.In this study,we performed a metabolite-based genome-wide association study and identified two biosynthetic gene clusters(BGC7 and BGC11)containing 12 genes involved in phenolamide metabolism,including four biosynthesis genes(two 4CL genes,one C3H gene,and one CPA gene),seven decoration genes(five AT genes and two UGT genes),and one transport protein gene(DTX29).Using gene co-expression network analysis we further discovered that SIMYB13 positively regulates the expression of two gene clusters,thereby promoting phe-nolamide accumulation.Genetic and physiological analyses showed that BGC7,BGC11 and SIMYB13 enhance drought tolerance by enhancing scavenging of reactive oxygen species and increasing abscisic acid content in tomato.Natural variation analysis suggested that BGC7,BGC11 and SIMYB13 were nega-tively selected during tomato domestication and improvement,leading to reduced phenolamide content and drought tolerance of cultivated tomato.Collectively,our study discovers a key mechanism of phenolamide biosynthesis and regulation in tomato and reveals that crop domestication and improve-ment shapes metabolic diversity to affect plant environmental adaptation.