Journal
MOLECULES
Volume 24, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/molecules24112111
Keywords
diketopiperazine; marine actinomycete; Streptomyces puniceus; Candida albicans; isocitrate lyase
Funding
- Basic Science Research Program through the National Research Foundation [NRF-2018R1D1A1B07043375]
- Ministry of Education, Science and Technology
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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 g/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 C-2-carbon-utilizing conditions.
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