en Related Fields Related Fields مقاله کامل Full Length/Original Article <strong>Background:</strong> The methylotrophic yeast <em>Pichia pastoris</em> is an appealing production host for a variety of recombinant proteins, including biologics. In this sense, various genetic- and non-genetic-based techniques have been implemented to improve the production efficiency of this expression platform<em>. </em>Loss of supression (<em>Los1</em>) encodes a non-essential nuclear tRNA exporter in <em>Saccharomyces cerevisiae</em>, which its deletion extends replicative lifespan. Herein, a <em>los1</em>-deficient strain of <em>P. pastoris</em> was generated and characterized. <strong>Methods: </strong>A gene disruption cassette was prepared and transformed into an anti-CD22-expressing strain of <em>P. pastoris</em>. A <em>&delta; los1 </em>mutant was isolated and confirmed. The drug sensitivity of the mutant was also assessed. The growth pattern and the level of anti-CD22 single-chain variable fragment (scFv) expression were compared between the parent and mutant strains. <strong>Results: </strong>The <em>los1</em> homologue was found to be a non-essential gene in <em>P. pastoris</em>. Furthermore, the susceptibility of <em>los1</em> deletion strain to protein synthesis inhibitors was altered. This strain showed an approximately 1.85-fold increase in the extracellular level of anti-CD22 scFv (<em>p</em> < 0.05). The maximum concentrations of total proteins secreted by <em>&delta; los1</em> and parent strains were 125 mg/L and 68 mg/L, respectively. <strong>Conclusion: </strong>The presented data suggest that the targeted disruption of <em>los1</em> homologue <em>in P. pastoris</em> can result in a higher expression level of our target protein. Findings of this study may improve the current strategies used in optimizing the productivity of recombinant <em>P. pastoris</em> strains. Aging, Longevity, Pichia pastoris, Recombinant proteins 255 264 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-857-2&slc_lang=en&sid=1 Najmeh Zarei 0000-0001-5634-7132 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Hosnieh Ghasemi v_khalaj@yahoo.com 0000-0002-4803-2912 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Mahsa Nayebhashemi v_khalaj@yahoo.com 0000-0002-3681-2233 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Mozhgan Zahmatkesh v_khalaj@yahoo.com 0000-0003-0838-9842 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Monire Jamalkhah 0000-0002-0737-6313 No Department of Biotechnology, College of Science, University of Tehran, Iran Nafiseh Moeinian 0000-0001-5634-7132 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Zahra Mohammadi 0000-0002-9034-5111 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Somayeh Enayati 0000-0002-5033-1954 No Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Vahid Khalaj v_khalaj@yahoo.com 0000-0003-1621-6394 Yes Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran