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Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids
Published on: January 26, 2012
Suvanine sesterterpenes from a tropical sponge Coscinoderma sp. inhibit isocitrate lyase in the glyoxylate cycle
So-Hyoung Lee1, Tae Hyung Won2, Heegyu Kim3
1Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea. awhee84@naver.com.
Abstract:
The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase (MLS). Mutants of Candida albicans lacking ICL are markedly less virulent in mice than the wild-type. Suvanine sesterterpenes (1-9) isolated from a tropical sponge Coscinoderma sp. were evaluated for their inhibitory activities toward recombinant ICL from C. albicans. These studies led to the identification of a potent ICL inhibitor, suvanine salt (2), which possesses a sodium counterion and displays an inhibitory concentration value (IC50) of 6.35 μM. The growth phenotype of ICL deletion mutants and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that compound 2 inhibits the ICL mRNA expression in C. albicans under C2-carbon-utilizing conditions. The present data highlight the potential for suvanine sesterterpenes treatment of C. albicans infections via inhibition of ICL activity.
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