Bacillimidazoles A-F, Imidazolium-Containing Compounds Isolated from a Marine Bacillus

Abstract

Chemical investigations of a marine sponge-associated Bacillus revealed six new imidazolium-containing compounds, bacillimidazoles A-F (1-6). Previous reports of related imidazolium-containing natural products are rare. Initially unveiled by timsTOF (trapped ion mobility spectrometry) MS data, extensive HRMS and 1D and 2D NMR analyses enabled the structural elucidation of 1-6. In addition, a plausible biosynthetic pathway to bacillimidazoles is proposed based on isotopic labeling experiments and invokes the highly reactive glycolytic adduct 2,3-butanedione. Combined, the results of structure elucidation efforts, isotopic labeling studies and bioinformatics suggest that 1-6 result from a fascinating intersection of primary and secondary metabolic pathways in Bacillus sp. WMMC1349. Antimicrobial assays revealed that, of 1-6, only compound six displayed discernible antibacterial activity, despite the close structural similarities shared by all six natural products.

Keywords: antibacterial; biosynthetic gene cluster; heterocycles; imidazolium; isotopic enrichment; marine-derived Bacillus.

Figure 1

Bruker timsTOF MS spectrum of the bioactive wells against MRSA. Peak/compound assignments are shown above each relevant signal.

Figure 2

Structures of bacillimidazoles A–F (1–6) with central imidazolium numberings indicated for each subgroup.

Figure 3

¹H–¹H COSY and key HMBC correlations of compounds 1–6.

Figure 4

Biosynthesis of bacillimidazoles. (a) Isotopic labeling of bacillimidazoles C (3) and E (5). Carbons highlighted with bold bonds and red spheres showed high levels of ¹³C incorporation. (b) Proposed biosynthetic pathway to compounds 1–6 calls for enzymatic production of tryptamine, phenethylamine and 2,3-butanedione (from glucose); all subsequent steps may proceed spontaneously.