Cyclotides as sustainable biopesticides: structure, function and agricultural potential

The ever-growing world population has escalated pressure on food production, leading to a dramatic rise in the use of chemical pesticides. Reliance on synthetic chemicals is not only hazardous to humans but also to the environment, highlighting the urgent need for eco-friendly alternatives. Biopesticides have emerged as a promising solution, with the global market for biostimulants and biopesticides projected to reach $30 billion within the next decade. Among these product classes, peptide-based biopesticides have gained considerable attention due to their high specificity, environmental compatibility, and efficacy. Several natural peptide families possess potency against plant pathogens. One such family is cyclotides, which are cyclic plant peptides that are involved in plant defence and have been extensively studied over the last few decades for their agricultural and pharmaceutical properties. Their exceptional stability, conferred by a head-to-tail cyclic backbone and cystine knot motif, enhances their resilience to formulation and storage and broadens their potential applications in agriculture. This review presents a comprehensive overview of cyclotides in the context of other biopesticide classes, highlighting their broad bioactivities, consensus sequence features linked to function, applications in agriculture, and their involvement in plant stress responses. We highlight key advances in the field over the past decade.