Inhibitory Effects of Diketopiperazines from Marine-Derived <i>Streptomyces puniceus</i> on the Isocitrate Lyase of <i>Candida albicans</i>

• Main Authors: Heegyu Kim, Ji-Yeon Hwang, Jongheon Shin, Ki-Bong Oh
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Molecules
• Subjects: diketopiperazine; marine actinomycete; <i>Streptomyces puniceus</i>; <i>Candida albicans</i>; isocitrate lyase
• Online Access: https://www.mdpi.com/1420-3049/24/11/2111

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 &#956;g/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 C₂-carbon-utilizing conditions.