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

Akira Ogita; Takeshi Doi; Shintaro Miyuki; Yoshinosuke Usuki; Yoshihiro Yamaguchi; Ken-ichi Fujita

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 30ºC. 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 37ºC. 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 esterasedependent 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.

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Evaluation of Fatty Acid Synthase as a Molecular Target for Stress-Dependent Fungicidal Activity of 1-Geranylgeranylpyridinium. (2020). Global Journal of Medical Research, 20(K2), 1-9. https://medicalresearchjournal.org/index.php/GJMR/article/view/1988

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References

K Pianalto, A Alspaugh (2016) New horizons in antifungal therapy. 2, 1-24.

Vicki Morrison (2006) Echinocandin antifungals: review and update. 4(2), 325-342.

Shunsuke Inoue, Hiroshi Qadota, Mikio Arisawa, Takahide Watanabe, Yoshikazu Ohya (1999) Prenylation of Rho1p Is Required for Activation of Yeast 1,3-β-Glucan Synthase. 274(53), 38119-38124.

David Levin (2005) Cell Wall Integrity Signaling inSaccharomyces cerevisiae. 69(2), 262-291.

Krishna Murthi, Susan Smith, Arthur Kluge, Gustave Bergnes, Patrick Bureau, Vivian Berlin (2003) Antifungal activity of a Candida albicans GGTase I inhibitor-Alanine conjugate. inhibition of Rho1p prenylation in C. albicans. 13(11), 1935-1937.

S Nishimura, S Matsunaga, M Shibazaki, K Suzuki, K Furihata, R Van Soest, N Fusetani, Massadine (2009) a novel geranylgeranyltransferase type 1 inhibitor from the marine sponge Stylissa aff. 5, 2255-2257.

Satoshi Sunami, Mitsuru Ohkubo, Takeshi Sagara, Jun Ono, Shuichi Asahi, Seita Koito, Hajime Morishima (2002) A new class of type I protein geranylgeranyltransferase (GGTase I) inhibitor. 12(4), 629-632.

Kiyotaka Machida, Toshio Tanaka, Ken-Ichi Fujita, Makoto Taniguchi (1998) Farnesol-Induced Generation of Reactive Oxygen Species via Indirect Inhibition of the Mitochondrial Electron Transport Chain in the Yeast Saccharomyces cerevisiae. 180(17), 4460-4465.

Kiyotaka Machida, Toshio Tanaka (1999) Farnesol‐induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F₀F₁‐ATPase in yeast. 462(1-2), 108-112.

P Voziyan, J Haug, G Melnykovych (2005) Mechanism of Farnesol Cytotoxicity: Further Evidence for the Role of PKC-Dependent Signal Transduction in Farnesol-Induced Apoptotic Cell Death. 212(2), 479-486.

Masahiro Hamada, Kyo-Ichi Nishio, Matsumi Doe, Yoshinosuke Usuki, Toshio Tanaka (2002) Farnesylpyridinium, an analog of isoprenoid farnesol, induces apoptosis but suppresses apoptotic body formation in human promyelocytic leukemia cells. 514(2-3), 250-254.

M Hamada, I Ohata, K-I Fujita, Y Usuki, A Ogita, J Ishiguro, T Tanaka (2006) Inhibitory activity of 1-farnesylpyridinium on the spatial control over the assembly of cell wall polysaccharide in Schizosaccharomyces pombe. 140, 851-859.

Toshio Tanaka, Haruka Hijioka, Ken-Ichi Fujita, Yoshinosuke Usuki, Makoto Taniguchi, Eiji Hirasawa (2004) Oxidative Stress-Dependent Inhibition of Yeast Cell Growth by Farnesylamine and Its Possible Relation to Amine Oxidase in the Mitochondrial Fraction. 98(6), 470-476.

Akira Ogita, Ken-Ichi Fujita, Yoshinosuke Usuki, Toshio Tanaka (2010) Targeted yeast vacuole disruption by polyene antibiotics with a macrocyclic lactone ring. 35(1), 89-92.

Masahiro Yutani, Akira Ogita, Yoshinosuke Usuki, Ken-Ichi Fujita, Toshio Tanaka (2011) Enhancement effect of N-methyl-N″-dodecylguanidine on the vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans. 64(7), 469-474.

H Iida, Y Yagawa, Y Anraku (1990) Essential role for induced Ca2+ influx followed by [Ca2+]i rise in maintaining viability of yeast cells late in the mating pheromone response pathway. A study of [Ca2+]i in single Saccharomyces cerevisiae cells with imaging of fura-2.. 265(22), 13391-13399.

M Iida, K Yamada, Y Nango, Y Yamaguchi, A Ogita, K Fujita, T Tanaka (2017) Vacuolar H + -ATPase subunit Vma1p functions as the molecular ligand in the vacuole-targeting fungicidal activity of polymyxin B. 163, 531-540.

L Mcalister, M Holland (1985) Differential expression of the three yeast glyceraldehyde-3-phosphate dehydrogenase genes.. 260(28), 15019-15027.

T Hori, N Nakamura, H Okuyama (1987) Possible involvement of acetyl coenzyme A carboxylase as well as fatty acid synthetase in the temperaturecontrolled synthesis of fatty acids in Saccharomyces cerevisiae. 101, 949-956.

Oksana Tehlivets, Kim Scheuringer, Sepp Kohlwein (2007) Fatty acid synthesis and elongation in yeast. 1771(3), 255-270.

M Ohba, R Sato, Y Yoshida, C Bieglmayer, H Ruis (1979) Mutant and immunological studies on the desaturation by yeast microsomes. 572, 352-362.

R Walenga, W Lands (1975) Effectiveness of various unsaturated fatty acids in supporting growth and respiration in Saccharomyces cerevisiae. 250(23), 9121-9129.

Hiroshi Funabashi, Akihiko Kawaguchi, Hiroshi Tomoda, Satoshi Ömura, Shigenobu Okuda, Shigeo Iwasaki (1989) Binding Site of Cerulenin in Fatty Acid Synthetase1. 105(5), 751-755.

C Klose, M Surma, M Gerl, F Meyenhofer, A Shevchenko, K Simons (2012) Flexibility of a eukaryotic lipidome -insights from yeast lipidomics. 7, e35063.

Michelle Leach, Leah Cowen (2014) Membrane Fluidity and Temperature Sensing Are Coupled via Circuitry Comprised of Ole1, Rsp5, and Hsf1 in Candida albicans. 13(8), 1077-1084.

A Brown, S Budge, D Kaloriti, A Tillmann, M Jacobsen, A Yin, I Ene, I Bohovych, D Sandai, S Kastora, J Potrykus, E Ballou, D Childers, S Shahana, M Leach (2014) Stress adaptation in a pathogenic fungus. 217, 144-155.

John Hallsworth (2018) Stress-free microbes lack vitality. 122(6), 379-385.

Abhishek Saxena, Ramakrishnan Sitaraman (2016) Osmoregulation in Saccharomyces cerevisiae via mechanisms other than the high-osmolarity glycerol pathway. 162(9), 1511-1526.

Long Nguyen, Joshua Nosanchuk (2011) The inhibitory effect of cerulenin to yeasts is fungicidal. 4(6), 631-632.

Cristina Viegas, M Rosa, Isabel Sá-Correia, Júlio Novais (1989) Inhibition of Yeast Growth by Octanoic and Decanoic Acids Produced during Ethanolic Fermentation. 55(1), 21-28.