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

Molecules

Heegyu Kim¹  Ki-Bong Oh¹  Jongheon Shin²  Ji-Yeon Hwang² 

[1] Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea;Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea;

关键词: diketopiperazine;    marine actinomycete;    Streptomyces puniceus;    Candida albicans;    isocitrate lyase;   

DOI  :  10.3390/molecules24112111

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown