Abstract: Phytophthora infestans, the causal agent of late blight in potato and tomato, is a historically devastating pathogen that continues to pose a major threat to global food security. Although conventional fungicides remain a cornerstone of crop protection, growing concerns over their environmental impact and long-term sustainability have driven the search for safer and more selective alternatives. In this context, next-generation fungicides with high specificity and minimal ecological footprint are urgently needed. This study introduces CP32, a small cyclic peptide, identified via yeast two-hybrid screening of a genetically encoded combinatorial peptide library, based on its specific interaction with the catalytic domain of the P. infestans enzyme Cellulose Synthase 2. CP32 exhibits anti-oomycete activity, effectively inhibits sporangial growth at low micromolar concentrations, and significantly reduces late blight symptoms on tomato leaves and entire plants. In silico docking analyses, supported by molecular and biochemical evidence, confirm that CP32 compromises cell-wall integrity by interfering with cellulose deposition and altering glucan composition. Furthermore, CP32 readily permeates the Phytophthora membrane and displays oomycete-static properties, while showing no detectable toxicity toward non-target organisms, such as bacteria, yeast, or plants. Collectively, these findings identify CP32 as a promising, targeted anti-oomycete agent with a unique mode of action, targeting the P. infestans cell wall, representing a valuable contribution to the development of sustainable strategies for the control of late blight.

Key words: cellulose synthase targeting, cell wall integrity, cyclic peptide, Phytophthora infestans