Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium

Authors

  • Akira Ogita

  • Takeshi Doi

  • Shintaro Miyuki

  • Yoshinosuke Usuki

  • Yoshihiro Yamaguchi

  • Ken-ichi Fujita

Keywords:

Saccharomyces cerevisiae; Candida albicans; fungal stress adaptation; geranylgeraniol derivative; fungicidal activity

Abstract

Among various isoprenoid compounds, 1-geranylgeranylpyridinium (GGPy) showed remarkable lethal effects on Saccharomyces cerevisiae cells similarly under hypo- and hyperosmotic conditions at 30#xBA;C. In addition to such osmotic stress, GGPy exhibited temperature-dependent lethal effects against S. cerevisiae and the pathogenic yeast Candida albicans at the human body temperature of 37#xBA;C. Fatty acid synthase (FAS) was identified as one of the GGPy-binding proteins and was considered a molecular target of GGPy in its inhibitory effect on the fungal stress adaptation. GGPy was not inhibitory to the activity of FAS assayed upon NADPH oxidation involved in acyl chain elongation by this multi-functional enzyme complex. Nevertheless, the lethality of GGPy was repressed in the medium where polyoxyethylene sorbitan monopalmitate (Tween 40) supplemented as the water-soluble and esterase-dependent source of palmitic acid. These findings may suggest that GGPy is permissive for acetyl unit incorporation into the growing chain of fatty acyl-CoA by FAS butis restrictive to its ultimate elongation to palmitoyl-CoA as a donor of the long-chain saturated fatty acid for the synthesis of stress-tolerant glycerophospholipids.

How to Cite

Akira Ogita, Takeshi Doi, Shintaro Miyuki, Yoshinosuke Usuki, Yoshihiro Yamaguchi, & Ken-ichi Fujita. (2020). Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium. Global Journal of Medical Research, 20(K2), 1–9. Retrieved from https://medicalresearchjournal.org/index.php/GJMR/article/view/1988

Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium

Published

2020-01-15