Feedback regulation of salicylic acid signaling by isochorismate synthase1 modulates camptothecin biosynthesis in Camptotheca acuminata

Salicylic acid (SA) signaling regulates specialized metabolite biosynthesis in plants, including camptothecin (CPT) accumulation. Previous works have demonstrated that SA enhanced CPT biosynthesis gene expression and increased CPT levels in Camptotheca acuminata. This study aimed to validate the feedback regulation of SA signaling in modulating CPT biosynthesis by ISOCHORISMATE SYNTHASE1 (CaICS1), an essential SA biosynthesis gene, in C. acuminata. Differential endogenous SA levels were generated by manipulating the expression of isochorismate transporter CaEDS5 for regulating SA signaling transduction. The results showed moderate SA signaling induced CaICS1 expression, while excessive SA reduced CaICS1 expression. This observation highlights a feedback mechanism whereby CaICS1 regulates SA signaling within an optimal range to control CPT biosynthesis genes’ transcription and CPT accumulation in C. acuminata. Overall, the findings elucidate the feedbackable role of CaICS1 in modulating SA signaling and downstream CPT metabolic engineering applications in Camptotheca plants.