Evidence map›Paper›PMID 42056837›Full record

ArticlePest management science2026

Discovery of the microtubule-severing protein as the target of antifungal compound heat-stable antifungal factor in Fusarium graminearum and rational design of novel inhibitors.

Jiamei Li, Wenchan Chen, Xin Jiang, Xinyi Cheng, Gaoge Xu, Yancun Zhao, Fengquan Liu, Yangyang Zhao

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Article in Pest management science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jiamei Li *School of Tropical Agriculture and Forestry, Hainan University, Haikou, China.
Wenchan Chen *College of Plant Protection, Hebei Agricultural University, Baoding, China.
Xin JiangSchool of Tropical Agriculture and Forestry, Hainan University, Haikou, China.
Xinyi ChengInstitute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
Gaoge XuInstitute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
Yancun ZhaoInstitute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
Fengquan LiuCollege of Agriculture, Guizhou University, Guiyang, China.
Yangyang ZhaoSchool of Tropical Agriculture and Forestry, Hainan University, Haikou, China.ORCID https://orcid.org/0000-0001-8826-9087

Funding

China Postdoctoral Science FoundationJiangsu Provincial Key Research and Development ProgramNational Natural Science Foundation of China
6 · The paper itself

Abstract

backgroundThe natural compound heat-stable antifungal factor (HSAF), produced by Lysobacter enzymogenes OH11, exhibits potent inhibitory activity against Fusarium graminearum and effectively controls Fusarium head blight, yet its mechanism remains unclear. Our previous work identified FGSG_09851, a microtubule-severing protein containing a conserved AAA (ATPases associated with diverse cellular activities) domain, binding to HSAF in F. graminearum. Here, we investigated the biological function of FGSG_09851 and explored its potential as an antifungal target.

resultsDeletion of FGSG_09851 led to a marked increase in HSAF resistance in F. graminearum (EC50: 1.602 ± 0.139 vs 0.787 ± 0.156 μg/mL for wild-type), and impaired mycelial growth, conidial germination, conidiation, and virulence. The ΔFGSG_09851 mutant exhibited sparse and disorganized microtubules, consistent with that observed under HSAF treatment. Molecular docking showed that HSAF binds to the active pocket of FGSG_09851 with a binding energy of -7.9 kcal/mol. Using structural features of known AAA+ ATPase inhibitors, we designed three compounds, AH-001, AH-002, and AH-003, which showed antifungal activity. Among them, AH-001 was the most potent, with inhibition rates of 25.5%, 39.5%, and 47.8% against F. graminearum at 120, 150, and 180 μg/mL, respectively. At 180 μg/mL, AH-002 and AH-003 achieved 35.4% and 32.9% inhibition.

conclusionThis study demonstrates that HSAF exerts its antifungal activity against F. graminearum by targeting the microtubule-severing protein FGSG_09851. Guided by this mechanism, we designed and synthesized novel AAA+ ATPase inhibitors with promising antifungal activity. These findings elucidate the mode of action of HSAF and establish microtubule-severing proteins as a promising target class for fungicide development. © 2026 Society of Chemical Industry.

Indexed as

Antifungal AgentsFungal ProteinsFungicides, IndustrialFusariumMicrotubulesMolecular Docking SimulationAntifungal AgentsFungal ProteinsFungicides, IndustrialAAA ATPase inhibitorsantifungalFusarium graminearummicrotubulemode of action

Identifiers

PMID42056837
PMCPMC13352289

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.