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The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii

Author

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  • Bernd M. Mitic

    (University of Natural Resources and Life Sciences, Vienna, Department of Biotechnology, Institute of Microbiology and Microbial Biotechnology, Muthgasse 18
    University of Natural Resources and Life Sciences, Vienna, Department of Chemistry, Institute of Analytical Chemistry, Muthgasse 18)

  • Christina Troyer

    (University of Natural Resources and Life Sciences, Vienna, Department of Chemistry, Institute of Analytical Chemistry, Muthgasse 18)

  • Lisa Lutz

    (University of Natural Resources and Life Sciences, Vienna, Department of Biotechnology, Institute of Microbiology and Microbial Biotechnology, Muthgasse 18
    Austrian Centre of Industrial Biotechnology (ACIB), Muthgasse 11)

  • Michael Baumschabl

    (University of Natural Resources and Life Sciences, Vienna, Department of Biotechnology, Institute of Microbiology and Microbial Biotechnology, Muthgasse 18
    Austrian Centre of Industrial Biotechnology (ACIB), Muthgasse 11)

  • Stephan Hann

    (University of Natural Resources and Life Sciences, Vienna, Department of Chemistry, Institute of Analytical Chemistry, Muthgasse 18
    Austrian Centre of Industrial Biotechnology (ACIB), Muthgasse 11)

  • Diethard Mattanovich

    (University of Natural Resources and Life Sciences, Vienna, Department of Biotechnology, Institute of Microbiology and Microbial Biotechnology, Muthgasse 18
    Austrian Centre of Industrial Biotechnology (ACIB), Muthgasse 11)

Abstract

The current climatic change is predominantly driven by excessive anthropogenic CO2 emissions. As industrial bioprocesses primarily depend on food-competing organic feedstocks or fossil raw materials, CO2 co-assimilation or the use of CO2-derived methanol or formate as carbon sources are considered pathbreaking contributions to solving this global problem. The number of industrially-relevant microorganisms that can use these two carbon sources is limited, and even fewer can concurrently co-assimilate CO2. Here, we search for alternative native methanol and formate assimilation pathways that co-assimilate CO2 in the industrially-relevant methylotrophic yeast Komagataella phaffii (Pichia pastoris). Using 13C-tracer-based metabolomic techniques and metabolic engineering approaches, we discover and confirm a growth supporting pathway based on native enzymes that can perform all three assimilations: namely, the oxygen-tolerant reductive glycine pathway. This finding paves the way towards metabolic engineering of formate and CO2 utilisation to produce proteins, biomass, or chemicals in yeast.

Suggested Citation

  • Bernd M. Mitic & Christina Troyer & Lisa Lutz & Michael Baumschabl & Stephan Hann & Diethard Mattanovich, 2023. "The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43610-7
    DOI: 10.1038/s41467-023-43610-7
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    References listed on IDEAS

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    1. Monica I. Espinosa & Ricardo A. Gonzalez-Garcia & Kaspar Valgepea & Manuel R. Plan & Colin Scott & Isak S. Pretorius & Esteban Marcellin & Ian T. Paulsen & Thomas C. Williams, 2020. "Adaptive laboratory evolution of native methanol assimilation in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Philipp Keller & Michael A. Reiter & Patrick Kiefer & Thomas Gassler & Lucas Hemmerle & Philipp Christen & Elad Noor & Julia A. Vorholt, 2022. "Generation of an Escherichia coli strain growing on methanol via the ribulose monophosphate cycle," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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