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[Display omitted] Phenolamides (PAs), a diverse group of specialized metabolites, including hydroxycinnamoylputrescine (HP), hydroxycinnamoylagmatine, and hydroxycinnamoyltryptamine, are important in plant resistance to biotic stress. However, the genes involved in the biosynthesis and modulation of PAs have not been fully elucidated. This study identified an HP biosynthetic gene cluster in rice (Oryza sativa) comprising one gene (OsODC) encoding a decarboxylase and two tandem-duplicated genes (OsPHT3 and OsPHT4) encoding putrescine hydroxycinnamoyl acyltransferases coexpressed in different tissues. OsODC catalyzes the conversion of ornithine to putrescine, which is used in HP biosynthesis involving OsPHT3 and OsPHT4. OsPHT3 or OsPHT4 overexpression causes HP accumulation and cell death and putrescine hydroxycinnamoyl acyltransferases (PHT) activity-dependent resistance against the fungal pathogen Magnaporthe oryzae. OsODC overexpression plants also confer enhanced resistance to M. oryzae. Notably, the basic leucine zipper transcription factor APIP5, a negative regulator of cell death, directly binds to the OsPHT4 promoter, repressing its transcription. Moreover, APIP5 suppression induces OsPHT4 expression and HP accumulation. Comparative genomic analysis revealed that the HP biosynthetic gene cluster is conserved in monocots. These results characterized a previously unidentified monocot-specific gene cluster that is involved in HP biosynthesis and contributes to defense and cell death in rice. [ABSTRACT FROM AUTHOR]