Cyclo(Val-Pro), a Potential Plant Immunomodulator, Confers Rice Blast Resistance via Circadian-Clock-Modulated Immune Activation and Metabolic Reprogramming

Abstract Rice blast, caused by Magnaporthe oryzae, is a devastating disease threatening global rice production, with current control strategies facing resistance and environmental risks. Small bioactive peptides have emerged as promising eco-friendly plant immunomodulators with low resistance risk for sustainable crop disease control. Here, we identified cyclic dipeptide cyclo(Val-Pro) as a potential plant immunomodulator with no direct fungicidal activity, which effectively conferred robust rice resistance to M. oryzae via promoting host intrinsic defense responses. Pre-treatment with cyclo(Val-Pro) activated salicylic acid (SA)- and jasmonic acid (JA)-mediated innate immunity, triggered reactive oxygen species (ROS) accumulation and callose deposition, and modulated core circadian clock genes in rice leaves. Transcriptomic and metabolomic analysis revealed that optimal blast resistance efficacy by cyclo(Val-Pro) pre-treatment at 14:00 was associated with circadian clock regulation and metabolic reprogramming. Specifically, cyclo(Val-Pro) rewired phenylpropanoid and tryptophan metabolism in rice leaves, and tryptamine was validated as a key functional downstream metabolite.