biostudies-literatureZhang LScience and Technology Commission of Shanghai MunicipalityShanghai Municipal Committee of Science and TechnologyShanghai Education Development Foundation and Shanghai Municipal Education CommissionNational Natural Science Foundation of ChinaInnovative research team of high-level local universities in Shanghaie2414844https://www.ebi.ac.uk/biostudies/studies/S-EPMC12079444biostudies-literatureUnknown12(18)Helicobacter pylori (H. pylori) is a group-1 definite pathogenic carcinogen that infects approximately half of the global population, yet no species-specific chemotherapy has yet been developed. It is previously discovered that H. pylori encodes an atypical dehydrogenase/isomerase FabX in the Type-II fatty acid biosynthesis pathway to produce unsaturated fatty acids (UFA) as well as superoxide (ROS). Here, it is demonstrated that FabX is essential for H. pylori growth and gastric colonization by retaining UFA synthesis and producing ROS, respectively, and is a species-specific anti-H. pylori drug target. The first small molecule inhibitor FBX-1991 against FabX, which inhibits the enzymatic activity with an IC₅₀ value of 0.158 × 10^-6 m in vitro, is developed. FBX-1991 Advanced science (Weinheim, Baden-Wurttemberg, Germany)Antagonist Targeting the Species-Specific Fatty Acid Dehydrogenase/Isomerase FabX for Anti-H. pylori Infection.PMC12079444220770812247707721TQ016221070678247397482073899SHSMU-ZDCX2021270220SG1622S11900600Zhang GBi HZhou LRuan XCai CHeng DZeng LZhang LHang XfalseAntagonist Targeting the Species-Specific Fatty Acid Dehydrogenase/Isomerase FabX for Anti-H. pylori Infection.Helicobacter pylori (H. pylori) is a group-1 definite pathogenic carcinogen that infects approximately half of the global population, yet no species-specific chemotherapy has yet been developed. It is previously discovered that H. pylori encodes an atypical dehydrogenase/isomerase FabX in the Type-II fatty acid biosynthesis pathway to produce unsaturated fatty acids (UFA) as well as superoxide (ROS). Here, it is demonstrated that FabX is essential for H. pylori growth and gastric colonization by retaining UFA synthesis and producing ROS, respectively, and is a species-specific anti-H. pylori drug target. The first small molecule inhibitor FBX-1991 against FabX, which inhibits the enzymatic activity with an IC₅₀ value of 0.158 × 10^-6 m in vitro, is developed. FBX-1991 2025-01-01T00:00:00Z2025 May2026-06-02T13:13:13.411Z2026-04-18T03:11:06.191ZS-EPMC120794444008985810.1002/advs.202414844