毕赤酵母对甲醇胁迫的响应及其对蛋白表达的影响

Research Progress on the Effect of Methanol Stress Response on Production of Heterologous Proteins in Pichia pastoris

醇氧化酶AOX1的启动子(P_(AOX1))被广泛应用于毕赤酵母表达外源蛋白,甲醇诱导可以使其表现出高效的转录活性,但甲醇诱导又可使毕赤酵母细胞产生过多的活性氧物质(ROS),诱发氧化胁迫响应和其他不利的生化生理响应,从而抑制蛋白的高效表达。综述了毕赤酵母对甲醇胁迫的响应及缓解甲醇胁迫的技术,并提出了UPR与甲醇胁迫响应交互作用机制的研究路线。

The promoter of alcohol oxidase AOX1(P_(AOX1))is widely used in Pichia pastoris to express heterologous proteins.Methanol induc-tion will lead to its high transcriptional activity.However,the induction with methanol gives rise to the abundance of reactive oxygen species(ROS)in Pichia pastoris cells,resulting in oxidative stress response and other adverse biochemical and physiological responses.Accordingly,high-efficiency expression of proteins would be inhibited.In this paper,the response of Pichia pastoris cells to methanol stress and the technique of alleviating methanol stress are reviewed.The authors look forward to the technical route of studying the mechanism of the interaction between UPR and methanol stress response,and the strategy of stimulating UPR to alleviate methanol stress is also raised.