Lenzimycins A and B, Metabolites With Antibacterial Properties From Brevibacillus sp. Associated With the Dung Beetle Onthophagus lenzii

Abstract

Symbiotic microorganisms associated with insects can produce a wide array of metabolic products, which provide an opportunity for the discovery of useful natural products. Selective isolation of bacterial strains associated with the dung beetle, <i>Onthophagus lenzii</i>, identified two strains, of which the antibiotic-producing <i>Brevibacillus</i> sp. PTH23 inhibited the growth of <i>Bacillus</i> sp. CCARM 9248, which is most closely related to the well-known entomopathogen, <i>Bacillus thuringiensis</i>. A comprehensive chemical investigation based on antibiotic activity discovered two new antibiotics, named lenzimycins A and B (<b>1</b>-<b>2</b>), which inhibited growth of <i>Bacillus</i> sp. CCARM 9248. The ¹H and ¹³C NMR, MS, MS/MS, and IR analyses elucidated the structures of <b>1</b> and <b>2</b>, which comprised a novel combination of fatty acid (12-methyltetradecanoic acid), glycerol, sulfate, and <i>N</i>-methyl ethanolamine. Furthermore, the acid hydrolysis of <b>1</b> revealed the absolute configuration of 12-methyltetradecanoic acid as 12<i>S</i> by comparing its optical rotation value with authentic (<i>R</i>)- and (<i>S</i>)-12-methyltetradecanoic acid. In addition to inhibition of <i>Bacillus</i> sp. CCARM 9248, lenzimycins A and B were found to inhibit the growth of some human pathogenic bacteria, including <i>Enterococcus faecium</i> and certain strains of <i>Enterococcus faecalis.</i> Furthermore, the present study elucidated that lenzimycins A and B activated a reporter system designed to detect the bacterial cell envelope stress, thereby indicating an activity against the integrity of the bacterial cell wall.