ArticleBMC genomics2022
Comparative transcriptome and metabolome analyses reveal the methanol dissimilation pathway of Pichia pastoris.
Article in BMC genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed.
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- Extracellular Expression and Diagnostic Potential of Dengue Virus Type 3 E Protein Domain III Through Codon Optimization in Komagataella phaffii.Molecular biotechnology · 2026Article
- Methanol feeding strategies for high-yield production of a collagen-based protein in Komagataella phaffii.Applied microbiology and biotechnology · 2025Article
- Efficient Expression of Lactone Hydrolase Cr2zen for Scalable Zearalenone Degradation inToxins · 2025Article
- Enhanced methanol tolerance and utilization in Pichia pastoris revealed by adaptive laboratory evolution.Journal of biological engineering · 2025Article
- Article
- Improvement of D-lactic acid production from methanol by metabolically engineeredMetabolic engineering communications · 2025Article
- Transcriptomic insights into methanol utilization in Pichia pastoris lacking AOX genes under co-feeding conditions.Archives of microbiology · 2025Article
- Metabolic engineering of Komagataella phaffii for enhanced 3-hydroxypropionic acid (3-HP) production from methanol.Journal of biological engineering · 2025Article
- What makesAntimicrobial agents and chemotherapy · 2024Article
- Hansenula polymorpha methanol metabolism genes enhance recombinant protein production in Komagataella phaffi.AMB Express · 2024Article
- Metabolic engineering of Komagataella phaffii for the efficient utilization of methanol.Microbial cell factories · 2024Article
- Transcriptomic and metabolomic correlation analysis: effect of initial SOFrontiers in microbiology · 2024Article
- Alternative PCR-Based Approaches for Generation ofMicroorganisms · 2023Article
- Effect and mechanism of signal peptide and maltose on recombinant type III collagen production in Pichia pastoris.Applied microbiology and biotechnology · 2023Article
- EngineeringSynthetic and systems biotechnology · 2023Article
- Improving Methanol Utilization by Reducing Alcohol Oxidase Activity and Adding Co-Substrate of Sodium Citrate inJournal of fungi (Basel, Switzerland) · 2023Article
- An integrated transcriptomic and metabolic phenotype analysis to uncover the metabolic characteristics of a genetically engineeredFrontiers in microbiology · 2023Article
- Properties, Physiological Functions and Involvement of Basidiomycetous Alcohol Oxidase in Wood Degradation.International journal of molecular sciences · 2022Review
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Abstract
backgroundPichia pastoris (Komagataella phaffii) is a model organism widely used for the recombinant expression of eukaryotic proteins, and it can metabolize methanol as its sole carbon and energy source. Methanol is oxidized to formaldehyde by alcohol oxidase (AOX). In the dissimilation pathway, formaldehyde is oxidized to CO
resultsThe transcriptome and metabolome of P. pastoris were determined under methanol cultivation when its dissimilation pathway cut off. Firstly, Δfld and Δfgh were significantly different compared to the wild type (GS115), with a 60.98% and 23.66% reduction in biomass, respectively. The differential metabolites between GS115 and Δfld were mainly enriched in ABC transporters, amino acid biosynthesis, and protein digestion and absorption. Secondly, comparative transcriptome between knockout and wild type strains showed that oxidative phosphorylation, glycolysis and the TCA cycle were downregulated, while alcohol metabolism, proteasomes, autophagy and peroxisomes were upregulated. Interestingly, the down-regulation of the oxidative phosphorylation pathway was positively correlated with the gene order of dissimilation pathway knockdown. In addition, there were significant differences in amino acid metabolism and glutathione redox cycling that raised our concerns about formaldehyde sorption in cells.
conclusionsThis is the first time that integrity of dissimilation pathway analysis based on transcriptomics and metabolomics was carried out in Pichia pastoris. The blockage of dissimilation pathway significantly down-regulates the level of oxidative phosphorylation and weakens the methanol assimilation pathway to the point where deficiencies in energy supply and carbon fixation result in inefficient biomass accumulation and genetic replication. In addition, transcriptional upregulation of the proteasome and autophagy may be a stress response to resolve formaldehyde-induced DNA-protein crosslinking.
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