Transcriptomic profiling of the yeast Komagataella phaffii in response to environmental alkalinization

Marcel Albacar, Abdelghani Zekhnini, Jorge Pérez-Valle, José L. Martínez, Antonio Casamayor, Joaquín Ariño*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

86 Downloads (Pure)

Abstract

Background
Adaptation to alkalinization of the medium in fungi involves an extensive remodeling of gene expression. Komagataella phaffii is an ascomycetous yeast that has become an organism widely used for heterologous protein expression. We explore here the transcriptional impact of moderate alkalinization in this yeast, in search of suitable novel promoters able to drive transcription in response to the pH signal.
Results
In spite of a minor effect on growth, shifting the cultures from pH 5.5 to 8.0 or 8.2 provokes significant changes in the mRNA levels of over 700 genes. Functional categories such as arginine and methionine biosynthesis, non-reductive iron uptake and phosphate metabolism are enriched in induced genes, whereas many genes encoding iron-sulfur proteins or members of the respirasome were repressed. We also show that alkalinization is accompanied by oxidative stress and we propose this circumstance as a common trigger of a subset of the observed changes. PHO89, encoding a Na+/Pi cotransporter, appears among the most potently induced genes by high pH. We demonstrate that this response is mainly based on two calcineurin-dependent response elements located in its promoter, thus indicating that alkalinization triggers a calcium-mediated signal in K. phaffii.
Conclusions
This work defines in K. phaffii a subset of genes and diverse cellular pathways that are altered in response to moderate alkalinization of the medium, thus setting the basis for developing novel pH-controlled systems for heterologous protein expression in this fungus.
Original languageEnglish
Article number63
JournalMicrobial Cell Factories
Volume22
Number of pages17
ISSN1475-2859
DOIs
Publication statusPublished - 2023

Keywords

  • Stress response
  • Oxidative stress
  • Promoter regulation
  • Protein production

Fingerprint

Dive into the research topics of 'Transcriptomic profiling of the yeast Komagataella phaffii in response to environmental alkalinization'. Together they form a unique fingerprint.

Cite this