2026-04-23 スウェーデン王立工科大学（KTH）
A comparison of two potatoes inoculated with Phytophthora infestans. Seven days after inoculation, the untreated potato (left) shows the characteristic late blight symptoms, while the potato treated with the peptide CS5 (right) shows no symptoms.
＜関連情報＞
- https://www.kth.se/en/om/nyheter/centrala-nyheter/a-new-way-to-stop-global-spread-of-pathogen-once-linked-to-ireland-s-great-famine-1.1471117
- https://www.sciencedirect.com/science/article/pii/S0141813026002655
持続的な病害防除のための環状ペプチド標的化によるPhytophthora infestansキチン合成酵素の阻害 Inhibition of Phytophthora infestans chitin synthase via cyclic peptide targeting for sustainable disease control
Sadia Fida Ullah, Lisa Kappel, Demetrio Marcianò, Kapali Suri, Stefano Rosa, Elena Marone Fassolo, Andrea Tagliani, Silvia Toffolatti, N. Arul Murugan, Paolo Pesaresi, Vincent Bulone, Simona Masiero, Vaibhav Srivastava
International Journal of Biological Macromolecules Available online: 20 January 2026
DOI:https://doi.org/10.1016/j.ijbiomac.2026.150339
Abstract
Phytophthora spp. are devastating plant pathogens causing significant economic losses in agriculture, but unlike true fungi, oomycetes have cell walls composed predominantly of cellulose and glucans, with little to no detectable chitin. Despite this, one to two putative chitin synthase (Chs) genes are present in Phytophthora spp. suggesting a functional role in its biology. In this study, we characterized the single chitin synthase of P. infestans (PiChs) to better understand its function and explore its potential as a target for novel fungicidal treatments. Unlike typical chitin synthases that generate long-chain chitin polymers, the recombinantly expressed PiChs predominantly synthesizes soluble chitooligosaccharides with degrees of polymerisation ranging from four to six. This finding provides a potential explanation for the undetectable chitin polymer in P. infestans cell wall analyses. Proteolytic processing was found to enhance PiChs activity, similar to observations in yeast and bacterial chitin synthases. PiChs exhibited sensitivity to Nikkomycin Z (NikZ), a well-characterized chitin synthase inhibitor, albeit with a higher IC₅₀ value compared to fungal heterologs. To enhance inhibition specificity, we developed a novel cyclic peptide inhibitor, named CS5, which exhibited stronger binding affinity and greater efficacy against PiChs compared to NikZ. Molecular docking, molecular dynamics simulations, and free energy calculations performed on both ligands revealed that CS5 competes with NikZ by binding to the same site on PiChs. In vitro and ex vivo assays confirmed that CS5 significantly impacted P. infestans growth, sporangial germination and host infection, supporting its potential as an alternative PiChs inhibitor. Our findings highlight the role of chitin synthase in P. infestans and its potential as a target for oomycete control. The development of tailored inhibitors such as CS5 presents an opportunity for sustainable disease management strategies, reducing reliance on broad-spectrum fungicides and addressing emerging resistance issues in agriculture.
