This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Donald, K. A. Articles by Fritz, I. B. Search for Related Content PubMed PubMed Citation Articles by Donald, K. A. Articles by Fritz, I. B. Agricola Articles by Donald, K. A. Articles by Fritz, I. B.

Next Article 

Appl. Environ. Microbiol., Sep 1997, 3341-3344, Vol 63, No. 9
Copyright © 1997, American Society for Microbiology

Effects of overproduction of the catalytic domain of 3-hydroxy-3- methylglutaryl coenzyme A reductase on squalene synthesis in Saccharomyces cerevisiae

KA Donald, RY Hampton and IB Fritz
Department of Cellular Physiology, Babraham Institute, Cambridge, United Kingdom. allen.donald@bbsrc.ac.uk

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-R) is the major rate-limiting enzyme of the mevalonate pathway in many organisms, including yeasts. In the yeast Saccharomyces cerevisiae, there are two isoenzymes of HMG-R (Hmg1p and Hmg2p). Both consist of an anchoring transmembrane domain and a catalytic domain. We have removed the known controlling features of HMG-R by overproducing the catalytic domain of Hmg1p. This overproduction leads to an enhancement of squalene production, implying that HMG-R has been deregulated. The enhancement is apparent under semianaerobic and aerobic conditions. Despite the increase in squalene production, the amount of ergosterol produced by the HMG-R-overproducing yeast was not increased. This result suggests the presence of another regulatory step between squalene and ergosterol formation. Squalene levels generated by cells overproducing the catalytic domain of HMG-R were estimated to be up to 10 times those produced by wild-type cells. The enhancement in squalene production coincided with a reduction in growth rate. This reduction may be a direct consequence of the buildup of high concentrations of squalene and presqualene intermediates of the pathway.

This article has been cited by other articles:

• Verwaal, R., Wang, J., Meijnen, J.-P., Visser, H., Sandmann, G., van den Berg, J. A., van Ooyen, A. J. J. (2007). High-Level Production of Beta-Carotene in Saccharomyces cerevisiae by Successive Transformation with Carotenogenic Genes from Xanthophyllomyces dendrorhous. Appl. Environ. Microbiol. 73: 4342-4350 [Abstract] [Full Text]  
• Loertscher, J., Larson, L. L., Matson, C. K., Parrish, M. L., Felthauser, A., Sturm, A., Tachibana, C., Bard, M., Wright, R. (2006). Endoplasmic Reticulum-Associated Degradation Is Required for Cold Adaptation and Regulation of Sterol Biosynthesis in the Yeast Saccharomyces cerevisiae.. Eukaryot Cell 5: 712-722 [Abstract] [Full Text]  
• Leivar, P., Gonzalez, V. M., Castel, S., Trelease, R. N., Lopez-Iglesias, C., Arro, M., Boronat, A., Campos, N., Ferrer, A., Fernandez-Busquets, X. (2005). Subcellular Localization of Arabidopsis 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase. Plant Physiol. 137: 57-69 [Abstract] [Full Text]  
• Cronin, S. R., Khoury, A., Ferry, D. K., Hampton, R. Y. (2000). Regulation of HMG-CoA Reductase Degradation Requires the P-Type ATPase Cod1p/Spf1p. J. Cell Biol. 148: 915-924 [Abstract] [Full Text]  
• Benko, A. L., Vaduva, G., Martin, N. C., Hopper, A. K. (2000). Competition between a sterol biosynthetic enzyme and tRNA modification in addition to changes in the protein synthesis machinery causes altered nonsense suppression. Proc. Natl. Acad. Sci. USA 97: 61-66 [Abstract] [Full Text]  
• Profant, D. A., Roberts, C. J., Koning, A. J., Wright, R. L. (1999). The Role of the 3-Hydroxy 3-Methylglutaryl Coenzyme A Reductase Cytosolic Domain in Karmellae Biogenesis. Mol. Biol. Cell 10: 3409-3423 [Abstract] [Full Text]