Stress in recombinant protein producing yeasts
Stress in recombinant protein producing yeasts
复制标题
DOI：
10.1016/j.jbiotec.2004.04.035
复制
发表时间：
2004-09-30
影响因子：
4.1
通讯作者：
Sauer, M
中科院分区：
文献类型：
--
作者：
Mattanovich, D;Gasser, B;Sauer, M
今天已经很好地确定，蛋白质的异源过表达与不同的应激反应有关。外源蛋白的高水平表达可能会通过竞争其他细胞过程的底物而直接限制其他细胞过程，或者如果它们的制造被阻止，则间接干扰代谢，从而诱导细胞的应激反应。特别是未折叠的蛋白质反应（UPR）在酿酒酵母（以及其他一些酵母）是有据可查的，其作用的表达水平的限制进行了讨论。内质网折叠限制的一个潜在后果是ER相关蛋白降解（ERAD），涉及胞质溶胶中的逆转位和衰变。高细胞密度发酵是重组酵母的典型工艺设计，其生长条件与细胞的自然环境相差甚远。因此，不同的环境应力可能会施加在宿主上。高渗透压、低pH和低温是典型的强制降解因素。尽管应激反应的分子途径已得到很好的表征，但缺乏关于应激反应对工业生产过程的影响的知识。因此，迄今为止进行的大多数代谢工程方法的目标是蛋白质折叠和分泌的改善，而只有少数针对一般应激敏感性的细胞工程的实例被公布。除了讨论在异源蛋白质生产的背景下，酵母菌的良好记录的应激反应，一些更投机的主题，如群体感应和凋亡的解决。(C)2004 Elsevier B.V.保留所有权利。
It is well established today that heterologous overexpression of proteins is connected with different stress reactions. The expression of a foreign protein at a high level may either directly limit other cellular processes by competing for their substrates, or indirectly interfere with metabolism, if their manufacture is blocked, thus inducing a stress reaction of the cell. Especially the unfolded protein response (UPR) in Saccharomyces cerevisiae (as well as some other yeasts) is well documented, and its role for the limitation of expression levels is discussed. One potential consequence of endoplasmatic reticulum folding limitations is the ER associated protein degradation (ERAD) involving retrotranslocation and decay in the cytosol. High cell density fermentation, the typical process design for recombinant yeasts, exerts growth conditions that deviate far from the natural environment of the cells. Thus, different environmental stresses may be exerted on the host. High osmolarity, low pH and low temperature are typical stress factors. Whereas the molecular pathways of stress responses are well characterized, there is a lack of knowledge concerning the impact of stress responses on industrial production processes. Accordingly, most metabolic engineering approaches conducted so far target at the improvement of protein folding and secretion, whereas only few examples of cell engineering against general stress sensitivity were published. Apart from discussing well-documented stress reactions of yeasts in the context of heterologous protein production, some more speculative topics like quorum sensing and apotosis are addressed. (C) 2004 Elsevier B.V. All rights reserved.