| Summary: | The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase, and plays an important role in the pathogenesis of microorganisms during infection. An <i>icl</i>-deletion mutant of <i>Candida albicans</i> exhibited reduced virulence in mice compared with the wild type. Five diketopiperazines, which are small and stable cyclic peptides, isolated from the marine-derived <i>Streptomyces puniceus</i> Act1085, were evaluated for their inhibitory effects on <i>C. albicans</i> ICL. The structures of these compounds were elucidated based on spectroscopic data and comparisons with previously reported data. Cyclo(L-Phe-L-Val) was identified as a potent ICL inhibitor, with a half maximal inhibitory concentration of 27 μg/mL. Based on the growth phenotype of the <i>icl</i>-deletion mutants and <i>icl</i> expression analyses, we demonstrated that cyclo(L-Phe-L-Val) inhibits the gene transcription of ICL in <i>C. albicans</i> under C<sub>2</sub>-carbon-utilizing conditions.
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