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首页> 外文期刊>Biotechnology Advances: An International Review Journal >Cultivation strategies to enhance productivity of Pichia pastoris: A review
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Cultivation strategies to enhance productivity of Pichia pastoris: A review

机译：提高毕赤酵母产量的栽培策略

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摘要

Pichia pastoris, a methylotrophic yeast, is an established system for the production of heterologous proteins, particularly biopharmaceuticals and industrial enzymes. To maximise and optimise the production of recombinant products, recent molecular research has focused on numerous issues including the design of expression vectors, optimisation of gene copy number, co-expression of secretory proteins such as chaperones, engineering of glycosylation and secretory pathways, etc. However, the physiological effects of different cultivation strategies are often difficult to separate from the molecular effects of the gene construct (e.g., cellular stress through overexpression or incorrect post-translational processing). Hence, overall system optimisation is difficult, even though it is urgently required in order to describe and understand the behaviour of new molecular constructs. This review focuses on particular aspects of recombinant protein production related to variations in biomass growth and their implications for strain design and screening, as well as on the concept of rational comparisons between cultivation systems for the development of specific production processes in bioreactors. The relationship between specific formation rates of secreted recombinant proteins, q(p), and specific growth rates, mu, has been analysed in a conceptual attempt to compare different systems, particularly those based on AOX1/methanol and GAP/glucose, and this has now evolved into a pivotal concept for bioprocess engineering of P. pastoris. (C) 2015 The Authors. Published by Elsevier Inc.
机译：巴斯德毕赤酵母是一种甲基营养型酵母，是一种用于生产异源蛋白质，特别是生物制药和工业酶的成熟系统。为了最大化和优化重组产品的生产，最近的分子研究集中在许多问题上，包括表达载体的设计，基因拷贝数的优化，诸如伴侣蛋白等分泌蛋白的共表达，糖基化和分泌途径的工程化等。但是，不同培养策略的生理效应通常很难与基因构建体的分子效应区分开（例如，由于过表达或错误的翻译后加工引起的细胞应激）。因此，即使为了描述和理解新分子构建体的行为而迫切需要进行总体系统优化也很困难。这篇综述着重于与生物量生长变化有关的重组蛋白生产的特定方面及其对菌株设计和筛选的影响，以及在培养系统之间进行合理比较以开发生物反应器中特定生产工艺的概念。为了比较不同的系统，特别是基于AOX1 /甲醇和GAP /葡萄糖的系统，在概念上进行了分析，分析了分泌的重组蛋白的特定形成速率q（p）与特定生长速率μ之间的关系。现在已经发展成为巴斯德毕赤酵母生物过程工程的关键概念。 （C）2015作者。由Elsevier Inc.发布

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