Expression of foreign genes in the yeast Pichia pastoris.
Expression of foreign genes in the yeast Pichia pastoris.
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DOI：
10.1007/0-306-47572-3_9
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
G. L. Cereghino;Anthony Jay J. Sunga;J. L. Cereghino;J. Cregg
中科院分区：
文献类型：
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作者：
G. L. Cereghino;Anthony Jay J. Sunga;J. L. Cereghino;J. Cregg
结论虽然P.巴斯德表达系统并不适合所有外源蛋白的生产，许多外源蛋白都与该系统兼容。对于这些蛋白质，在这种酵母中生产具有重大优势。相对于高等真核表达系统，培养成本较低，产量（外来蛋白/L培养基）通常较高，并且对于分泌蛋白，培养基中产物的初始纯度较高。相对于细菌表达系统，使用 P 回收具有生物活性形式的真核外源蛋白的机会明显更高。虽然市场上很少有由巴斯德毕赤酵母生产的主要人类药物，但有几种正处于临床试验阶段，包括抗肿瘤药物血管抑制素和内皮抑素 (44)。此外，P.巴斯德氏菌是唯一可供学术研究人员作为完整试剂盒使用的低等真核表达系统之一（参见 Invitrogen 目录）。该系统的最新改进，包括新的标记宿主组合和替代启动子，应该会增加这种甲基营养宿主可以产生的蛋白质的范围。随着越来越多的蛋白质在 P 中成功（或不成功）地合成。毕赤酵母中，与特定类别蛋白质的最佳表达相关的参数将得到更好的定义。
ConclusionAlthough theP. pastorisexpression system is not suitable for the production of all foreign proteins, many are compatible with the system. For these proteins, there are major advantages to production in this yeast. Relative to higher eukaryotic expression systems, culturing costs are lower, yields (foreign protein/L of culture medium) are usually higher, and for secreted proteins, the initial purity of the product in the culture medium is higher. Relative to bacterial expression systems, the chances of recovering a eukaryotic foreign protein in its biologically active form are significantly higher withP. pastoris.Although few majorP.pastoris- producedhuman Pharmaceuticals are on the market, several are in the clinical trial pipeline, including the anti-tumor drugs angiostatin and endostatin (44). In addition,P. pastorisis one of the only lower eukaryotic expression systems that is available to academic researchers as a complete kit (see Invitrogen catalog). Recent improvements in the system, including new marker host combinations and alternative promoters, should increase the range of proteins that can be produced by this methylotrophic host. As more proteins are successfully (or unsuccessfully) synthesized inP. pastoris, parameters involved with the optimal expression of specific classes of proteins will become better defined.