Bacillaenes: Decomposition Trigger Point and Biofilm Enhancement in <i>Bacillus</i>

Abstract

Bacillaenes are a class of poly-unsaturated enamines produced by <i>Bacillus</i> strains that are notoriously unstable toward light, oxygen, and normal temperature. Herein, in an in-depth study of this highly unstable chemotype, the stability and biological function of bacillaenes were investigated. The structure change of the bacillaene scaffold was tracked by time-course ¹H NMR data analysis coupled with the differential analysis of 2D-NMR spectra method, which was demonstrated to be a "domino" effect triggered by 4',5'-<i>cis</i> (<b>2</b> and <b>3</b>) configuration rearranged to trans (<b>2a</b> and <b>3a</b>). These findings provide the possibility for stabilizing the bacillaene scaffold by chemical modification of its trigger points. In the biofilm assay, compounds <b>1</b> and <b>2</b> accelerated self-biofilm formation in <i>Bacillus methylotrophicus</i> B-9987 at low concentrations of 1.0 and 0.1 μg/mL. Interestingly, bacillaenes play dual roles as antibiotic and biofilm enhancers in a dose-dependent manner, both of which serve in the self-protection of <i>Bacillus</i>.