Inhibitory Effects of Nitrogenous Metabolites from a Marine-Derived <i>Streptomyces bacillaris</i> on Isocitrate Lyase of <i>Candida albicans</i>

Abstract

Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 μM) and weak (IC50 = 190.45 μM) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C2-carbon-utilizing conditions.

Keywords

• <i>Streptomyces bacillaris</i>
• bacillimide
• bacillapyrrole
• isocitrate lyase
• <i>Candida albicans</i>