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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 P  LRA3   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 P  LRA3   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.

amb express

Decreased expression of LRA4, a key gene involved in rhamnose metabolism, caused up-regulated expression of the genes in this pathway and autophagy in Pichia pastoris