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bioRxiv · 10.1101/2022.10.05.511033

Discovery and biosynthesis of imidazolium antibiotics from a probiotic Bacillus licheniformis

Ham, S. L.·Lee, T. H.·Kim, K. J.·Kim, J. H.·Hwang, S. J.·Lee, S. H.·Lee, W.·Kim, C. S.
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Abstract

Antibiotic resistance is one of the worlds most urgent public health problems and therefore novel antibiotics to kill drug-resistant bacteria are desperately needed. So far, natural product-derived small molecules have been the major sources for new antibiotics. Here we describe a family of antibacterial metabolites isolated from a probiotic bacterium Bacillus licheniformis. Cross-streaking assay followed by activity-guided isolation yielded a novel antibacterial metabolite bacillimidazole G, which possesses a rare imidazolium ring in the structure, showing MIC values of 0.7-2.6 g/mL against human pathogenic Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and a lipopolysaccharide(LPS)-lacking Acinetobacter baumannii {Delta}lpxC. Bacillimidazole G also lowered MICs of colistin, a Gram-negative antibiotic, up to 8-fold against wild-type E. coli MG1655 and Acinetobacter baumannii. We propose biosynthetic pathway of the characterized metabolites based on the precursor-feeding studies, chemical biological approach, biomimetic total synthesis, and biosynthetic genes knockout method. TOC/Abstract Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=34 SRC="FIGDIR/small/511033v1_ufig1.gif" ALT="Figure 1"> View larger version (8K): org.highwire.dtl.DTLVardef@184f545org.highwire.dtl.DTLVardef@2a69eorg.highwire.dtl.DTLVardef@8cf13org.highwire.dtl.DTLVardef@530001_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Ham, S. L., Lee, T. H., Kim, K. J., Kim, J. H., Hwang, S. J., Lee, S. H., Lee, W., Kim, C. S.. 2022-10-05. Discovery and biosynthesis of imidazolium antibiotics from a probiotic Bacillus licheniformis. https://doi.org/10.1101/2022.10.05.511033

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