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Applied and Environmental Microbiology, December 2008, p. 7130-7137, Vol. 74, No. 23
0099-2240/08/$08.00+0     doi:10.1128/AEM.00955-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

SOD1, a New Kluyveromyces lactis Helper Gene for Heterologous Protein Secretion{triangledown}

S. Raimondi,1 E. Zanni,2,3 C. Talora,4 M. Rossi,1 C. Palleschi,2,3 and D. Uccelletti2,3*

Department of Chemistry, University of Modena and Reggio Emilia, Modena, Italy,1 Istituto Pasteur-Fondazione Cenci Bolognetti, La Sapienza, Rome, Italy,2 Department of Developmental and Cell Biology, University of Rome La Sapienza, Rome, Italy,3 Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy4

Received 27 April 2008/ Accepted 21 September 2008

Bottlenecks in protein expression and secretion often limit the development of industrial processes. By manipulating chaperone and foldase levels, improvements in yeast secretion were found for a number of proteins. Recently, sustained endoplasmic reticulum stress, occurring due to recombinant protein production, was reported to cause oxidative stress in yeast. Saccharomyces cerevisiae cells are able to trigger an adaptive response to oxidative-stress conditions, resulting in the upregulation of both primary and secondary antioxidant defenses. SOD1 encodes for a superoxide dismutase that catalyzes the dismutation of superoxide anions (O2–) into oxygen and hydrogen peroxide. It is a Cu2+/Zn2+ metalloenzyme and represents an important antioxidant defense in nearly all aerobic and aerotolerant organisms. We found that overexpression of the Kluyveromyces lactis SOD1 (KlSOD1) gene was able to increase the production of two different heterologous proteins, human serum albumin (HSA) and glucoamylase from Arxula adeninivorans. In addition, KlSOD1 overexpression led to a significant decrease in the amount of reactive oxygen species (ROS) that originated during protein production. The yield of HSA also increased when K. lactis cells were grown in the presence of the antioxidant agent ascorbic acid and decreased when cells were challenged with menadione, a ROS generator compound. Moreover, we observed that, in high-osmolarity medium, cells overexpressing KlSOD1 showed higher growth rates than control cells. Our results thus further support the notion that the production of some heterologous proteins may be improved by manipulating genes involved in general stress responses.

* Corresponding author. Mailing address: Dept. of Developmental and Cell Biology, University of Rome La Sapienza, P.le Aldo Moro, 5, 00185 Rome, Italy. Phone: 39-0649912258. Fax: 39-0649912321. E-mail: daniela.uccelletti{at}uniroma1.it

{triangledown} Published ahead of print on 3 October 2008.

Applied and Environmental Microbiology, December 2008, p. 7130-7137, Vol. 74, No. 23
0099-2240/08/$08.00+0     doi:10.1128/AEM.00955-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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