In a previous study, we developed Pichia pastoris GS115m, an engineered strain with decreased expression of one key gene, LRA4, in rhamnose metabolism. P. pastoris GS115m/LacB was subsequently constructed via introducing a β-galactosidase gene, LacB, under the control of rhamnose-inducible PLRA3 into P. pastoris GS115m. P. pastoris GS115m/LacB greatly improved recombinant protein production relative to the parental strain (P. pastoris GS115/LacB). In the present study, transcriptomes of P. pastoris GS115m/LacB and P. pastoris GS115/LacB grown in YPR medium were analyzed. P. pastoris GS115m/LacB was found to suffer from the mild carbon source starvation. To attenuate the starvation stress, P. pastoris GS115m/LacB attempted to enhance rhamnose metabolism by elevating the transcription levels of rhamnose-utilization genes LRA1-3 and RhaR. The transcription level of LacB under the control of PLRA3 thereby increased, resulting in the improved production of recombinant protein in P. pastoris GS115m/LacB. It was also revealed that P. pastoris GS115m/LacB cells coped with carbon starvation mostly via autophagy.

中文翻译：

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LRA4（鼠李糖代谢中的一个关键基因）的表达降低，导致该途径中该基因的表达上调并在巴斯德毕赤酵母中自噬。

在先前的研究中，我们开发了巴斯德毕赤酵母GS115m，这是一种工程菌，鼠李糖代谢中一个关键基因LRA4的表达降低。随后通过在鼠李糖诱导的PLRA3的控制下将β-半乳糖苷酶基因LacB引入巴斯德毕赤酵母GS115m中来构建巴斯德毕赤酵母GS115m / LacB。相对于亲本菌株（P. pastoris GS115 / LacB），巴斯德毕赤酵母GS115m / LacB大大提高了重组蛋白的生产。在本研究中，分析了在YPR培养基中生长的巴斯德毕赤酵母GS115m / LacB和巴斯德毕赤酵母GS115 / LacB的转录组。发现巴斯德毕赤酵母GS115m / LacB患有轻度碳源饥饿。为了减轻饥饿压力，巴斯德毕赤酵母GS115m / LacB试图通过提高鼠李糖利用基因LRA1-3和RhaR的转录水平来增强鼠李糖代谢。因此，在PLRA3的控制下，LacB的转录水平增加，导致巴斯德毕赤酵母GS115m / LacB中重组蛋白的产量提高。还发现巴斯德毕赤酵母GS115m / LacB细胞主要通过自噬来应对碳饥饿。