Discovery of Natural FabH Inhibitors Using an Immobilized Enzyme Column and Their Antibacterial Activity against Xanthomonas oryzae pv. oryzae
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Abstract
β-Ketoacyl-acyl carrier protein synthase III (KAS III, FabH) is essential for bacterial fatty acid biosynthesis. Recent studies indicate that FabH can be a potential target for bactericide development. In the present study, an immobilized FabH column was developed and used to screen FabH inhibitors from complex natural product extracts. Combined with HPLC, four secondary metabolites, alternariol (1), altenuisol (2), alterlactone (3), and dehydroaltenusin (4), were site-directed, isolated, and identified from the crude extract of Alternaria alternata ZHJG5. These compounds showed inhibitory activities on FabH of Xanthomonas oryzae pv. oryzae (Xoo) with IC50 values from 29.5 to 74.1 μM and also displayed a varying degree of antibacterial activities against Xoo with minimal inhibitory concentration values from 4 to 64 μg/mL. Molecular modeling was then used to picture how the compounds interact with XooFabH. Two inhibitors, compounds 1 and 3, exhibited significant bactericidal activity against rice bacterial leaf blight with a protective efficiency of 66.2 and 82.5% at the concentration of 200 μg/mL, respectively, suggesting that they could be lead candidates to develop novel bactericides.
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