title: In Pichia pastoris, growth rate regulates protein synthesis and secretion, mating and stress response.
abstract: Protein production in yeasts is related to the specific growth rate μ. To elucidate on this correlation, we studied the transcriptome of Pichia pastoris at different specific growth rates by cultivating a strain secreting human serum albumin at μ = 0.015 to 0.15 h(-1) in glucose-limited chemostats. Genome-wide regulation revealed that translation-related as well as mitochondrial genes were upregulated with increasing μ, while autophagy and other proteolytic processes, carbon source-responsive genes and other targets of the TOR pathway as well as many transcriptional regulators were downregulated at higher μ. Mating and sporulation genes were most active at intermediate μ of 0.05 and 0.075 h(-1) . At very slow growth (μ = 0.015 h(-1) ) gene regulation differs significantly, affecting many transporters and glucose sensing. Analysis of a subset of genes related to protein folding and secretion reveals that unfolded protein response targets such as translocation, endoplasmic reticulum genes, and cytosolic chaperones are upregulated with increasing growth rate while proteolytic degradation of secretory proteins is downregulated. We conclude that a high μ positively affects specific protein secretion rates by acting on multiple cellular processes.
authors: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
authors: Corinna
authors: C
authors: Rebnegger
authors: Alexandra B
authors: AB
authors: Graf
authors: Minoska
authors: M
authors: Valli
authors: Matthias G
authors: MG
authors: Steiger
authors: Brigitte
authors: B
authors: Gasser
authors: Michael
authors: M
authors: Maurer
authors: Diethard
authors: D
authors: Mattanovich
mesh_terms: D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics* / Q000502:physiology*; D008954:Models, Biological; D010843:Pichia / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins; D056811:Unfolded Protein Response
chemical_list: D005656:Fungal Proteins; D011994:Recombinant Proteins
keywords: Filamentous growth; Recombinant protein secretion; Specific growth rate; Unfolded protein response; Yeast