The effect of hypoxia on the lipidome of recombinant Pichia pastoris

Microbial Cell Factories
Núria AdelantadoPau Ferrer

Abstract

Cultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia. To improve our understanding of the interplay between lipid metabolism, UPR and protein secretion, the lipidome of a P. pastoris strain producing an antibody fragment was studied under hypoxic conditions. Furthermore, lipid composition analyses were combined with previously available transcriptomic datasets to further understand the impact of hypoxia on lipid metabolism. Chemostat cultures operated under glucose-limiting conditions under normoxic and hypoxic conditions were analyzed in terms of intra/extracellular product distribution and lipid composition. Integrated analysis of lipidome and transcriptome datasets allowed us to demonstrate an important remode...Continue Reading

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Citations

Sep 22, 2017·FEMS Yeast Research·Richard J ZahrlBrigitte Gasser
Jul 17, 2020·Frontiers in Bioengineering and Biotechnology·Miguel Angel Nieto-TaypeFrancisco Valero
May 4, 2021·Frontiers in Microbiology·Xinyi ChenHu Liu

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Methods Mentioned

BETA
protein folding
PCR
ELISA
flow cytometry

Software Mentioned

Excel Analysis ToolPak
QuantaSoft

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