Abstract
Chemical communication, a universal mode among the interactive members within dynamic plant-microbiome systems, fundamentally drives coevolutionary trajectories. Emerging evidence suggests the critical role of epigenetic regulation in chemical communication, though its mechanistic insights are yet not well understood, a gap that has limited the precise mining of microbiomes function in modern agriculture. Here, we synthesize recent findings from chemistry to epigenetics to illuminate the overlooked epigenetic landscape in plant-microbiome chemical communication. Revisiting the traditional plant-pathogen interaction model and a more complex ternary model involving the plant resident microbiota, we not only present knowledge gaps but also critically dissect the paradoxical roles of resident microbiota by proposing four chemo-epigenetic patterns that fine-tune the interactions among plants, resident microbiota and pathogens. Further, Intelligent Click Chemistry, an innovative interdisciplinary strategy integrating click chemistry and artificial intelligence, is proposed and discussed, with the aim of unraveling the complex chemo-epigenetic events underlying plant-microbiome chemical communication. Untangling the epigenetic landscape underpinning plant-microbiome chemical communication would enable the strategic and precise exploitation of beneficial microbial traits and suppression of detrimental interactions for sustainable agriculture.