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Journal of Bacteriology, March 2002, p. 1395-1401, Vol. 184, No. 5
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.5.1395-1401.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of a Squalene Epoxidase Inhibitor, Terbinafine, on Ether Lipid Biosyntheses in a Thermoacidophilic Archaeon, Thermoplasma acidophilum

*** Takahide Kon,1 Naoki Nemoto,2 Tairo Oshima,2 and Akihiko Yamagishi2*

Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba, Tokyo 153-8902,1 Department of Molecular Biology, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan2

Received 6 August 2001/ Accepted 28 November 2001

The archaeal plasma membrane consists mainly of diether lipids and tetraether lipids instead of the usual ester lipids found in other organisms. Although a molecule of tetraether lipid is thought to be synthesized from two molecules of diether lipids, there is no direct information about the biosynthetic pathway(s) or intermediates of tetraether lipid biosynthesis. In this study, we examined the effects of the fungal squalene epoxidase inhibitor terbinafine on the growth and ether lipid biosyntheses in the thermoacidophilic archaeon Thermoplasma acidophilum. Terbinafine was found to inhibit the growth of T. acidophilum in a concentration-dependent manner. When growing T. acidophilum cells were pulse-labeled with [2-14C]mevalonic acid in the presence of terbinafine, incorporation of radioactivity into the tetraether lipid fraction was strongly suppressed, while accumulation of radioactivity was noted at the position corresponding to diether lipids, depending on the concentration of terbinafine. After the cells were washed with fresh medium and incubated further without the radiolabeled substrate and the inhibitor, the accumulated radioactivity in the diether lipid fraction decreased quickly while that in the tetraether lipids increased simultaneously, without significant changes in the total radioactivity of ether lipids. These results strongly suggest that terbinafine inhibits the biosynthesis of tetraether lipids from a diether-type precursor lipid(s). The terbinafine treatment will be a tool for dissecting tetraether lipid biosynthesis in T. acidophilum.

* Corresponding author. Mailing address: Department of Molecular Biology, Tokyo University of Pharmacy and Life Science, 1432 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Phone: 81-426-76-7139. Fax: 81-426-76-7145. E-mail: yamagish{at}LS.toyaku.ac.jp.

Journal of Bacteriology, March 2002, p. 1395-1401, Vol. 184, No. 5
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.5.1395-1401.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koga, Y., Morii, H. (2007). Biosynthesis of Ether-Type Polar Lipids in Archaea and Evolutionary Considerations. Microbiol. Mol. Biol. Rev. 71: 97-120 [Abstract] [Full Text]  
  • Hemmi, H., Shibuya, K., Takahashi, Y., Nakayama, T., Nishino, T. (2004). (S)-2,3-Di-O-geranylgeranylglyceryl Phosphate Synthase from the Thermoacidophilic Archaeon Sulfolobus solfataricus: MOLECULAR CLONING AND CHARACTERIZATION OF A MEMBRANE-INTRINSIC PRENYLTRANSFERASE INVOLVED IN THE BIOSYNTHESIS OF ARCHAEAL ETHER-LINKED MEMBRANE LIPIDS. J. Biol. Chem. 279: 50197-50203 [Abstract] [Full Text]  
  • Nemoto, N., Oshima, T., Yamagishi, A. (2003). Purification and Characterization of Geranylgeranylglyceryl Phosphate Synthase from a Thermoacidophilic Archaeon, Thermoplasma acidophilum. J Biochem 133: 651-657 [Abstract] [Full Text]  


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