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Gewählte Publikation:

Rebnegger, C; Graf, AB; Valli, M; Steiger, MG; Gasser, B; Maurer, M; Mattanovich, D.
(2014): In Pichia pastoris, growth rate regulates protein synthesis and secretion, mating and stress response
BIOTECHNOL J. 2014; 9(4): 511-525. FullText FullText_BOKU

Abstract:
Protein production in yeasts is related to the specific growth rate . 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 = 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 , 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 . Mating and sporulation genes were most active at intermediate of 0.05 and 0.075 h(-1). At very slow growth ( = 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 positively affects specific protein secretion rates by acting on multiple cellular processes.
Autor*innen der BOKU Wien:
Gasser Brigitte
Mattanovich Diethard
Rebnegger Corinna
Steiger Matthias
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Fungal Proteins/genetics*
Fungal Proteins/metabolism
Gene Expression Regulation, Fungal/genetics*
Gene Expression Regulation, Fungal/physiology*
Models, Biological
Pichia/genetics*
Pichia/physiology*
Recombinant Proteins
Unfolded Protein Response

Find related publications in this database (Keywords)
Filamentous growth
Recombinant protein secretion
Specific growth rate
Unfolded protein response
Yeast


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