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- Title
Inhibitory Effects of Diketopiperazines from Marine-Derived Streptomyces puniceus on the Isocitrate Lyase of Candida albicans.
- Authors
Kim, Heegyu; Hwang, Ji-Yeon; Shin, Jongheon; Oh, Ki-Bong; Duval, Raphaël E.
- Abstract
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 icl-deletion mutant of Candida albicans exhibited reduced virulence in mice compared with the wild type. Five diketopiperazines, which are small and stable cyclic peptides, isolated from the marine-derived Streptomyces puniceus Act1085, were evaluated for their inhibitory effects on C. albicans 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 icl-deletion mutants and icl expression analyses, we demonstrated that cyclo(L-Phe-L-Val) inhibits the gene transcription of ICL in C. albicans under C2-carbon-utilizing conditions.
- Subjects
DIKETOPIPERAZINES; STREPTOMYCES; CANDIDA albicans; CYCLIC peptides
- Publication
Molecules, 2019, Vol 24, Issue 11, p2111
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules24112111