Author:
Jiao Jian,Wang Shuai,Tian Hui,Xu Xinxin,Zhang Yuhong,Liu Bo,Zhang Wei
Abstract
AbstractIn 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.
Funder
National Natural Science Foundation of China
National Transgenic Major Program
Central Public-interest Scientific Institution Basal Research Fund, Chinese Academy of Fishery Sciences
Publisher
Springer Science and Business Media LLC
Subject
Applied Microbiology and Biotechnology,Biophysics