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N-hypermannose glycosylation disruption enhances recombinant protein production by regulating secretory pathway and cell wall integrity in Saccharomyces cerevisiae

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논문

N-hypermannose glycosylation disruption enhances recombinant protein production by regulating secretory pathway and cell wall integrity in Saccharomyces cerevisiae

학술지

Scientific reports

저자명

Tang, Hongting; Wang, Shenghuan; Wang, Jiajing; Song, Meihui; Xu, Mengyang; Zhang, Mengying; Shen, Yu; Hou, Jin; Bao, Xiaoming

초록

<P><I>Saccharomyces cerevisiae</I> is a robust host for heterologous protein expression. The efficient expression of cellulases in <I>S. cerevisiae</I> is important for the consolidated bioprocess that directly converts lignocellulose into valuable products. However, heterologous proteins are often <I>N</I>-hyperglycosylated in <I>S. cerevisiae</I>, which may affect protein activity. In this study, the expression of three heterologous proteins, &beta;-glucosidase, endoglucanase and cellobiohydrolase, was found to be <I>N</I>-hyperglycosylated in <I>S. cerevisiae</I>. To block the formation of hypermannose glycan, these proteins were expressed in strains with deletions in key Golgi mannosyltransferases (Och1p, Mnn9p and Mnn1p), respectively. Their extracellular activities improved markedly in the <I>OCH1</I> and <I>MNN9</I> deletion strains. Interestingly, truncation of the <I>N</I>-hypermannose glycan did not increase the specific activity of these proteins, but improved the secretion yield. Further analysis showed <I>OCH1</I> and <I>MNN9</I> deletion up-regulated genes in the secretory pathway, such as protein folding and vesicular trafficking, but did not induce the unfolded protein response. The cell wall integrity was also affected by <I>OCH1</I> and <I>MNN9</I> deletion, which contributed to the release of secretory protein extracellularly. This study demonstrated that mannosyltransferases disruption improved protein secretion through up-regulating secretory pathway and affecting cell wall integrity and provided new insights into glycosylation engineering for protein secretion.</P>

발행연도

2016

발행기관

Nature Publishing Group

라이선스

cc-by

ISSN

2045-2322

6

페이지

pp.25654

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논문; 2016-05-09

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