Role of Dissimilative Pathway of <i>Komagataella phaffii</i> (<i>Pichia pastoris</i>): Formaldehyde Toxicity and Energy Metabolism


Berrios, Julio, Theron, Chrispian W ORCID: 0000-0002-8522-6417, Steels, Sebastien, Ponce, Belen, Velastegui, Edgar, Bustos, Cristina, Altamirano, Claudia and Fickers, Patrick (2022) Role of Dissimilative Pathway of <i>Komagataella phaffii</i> (<i>Pichia pastoris</i>): Formaldehyde Toxicity and Energy Metabolism. MICROORGANISMS, 10 (7). 1466-.

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Abstract

<i>Komagataella phaffii</i> (aka <i>Pichia pastoris</i>) is a yeast able to grow in methanol as the sole carbon and energy source. This substrate is converted into formaldehyde, a toxic intermediary that can either be assimilated to biomass or dissimilated to CO<sub>2</sub> through the enzymes formaldehyde dehydrogenase (FLD) and formate dehydrogenase, also producing energy in the form of NADH. The dissimilative pathway has been described as an energy producing and a detoxifying route, but conclusive evidence has not been provided for this. In order to elucidate this theory, we generated mutants lacking the FLD activity (Δ<i>fld1</i>) and used flux analysis to evaluate the metabolic impact of this disrupted pathway. Unexpectedly, we found that the specific growth rate of the Δ<i>fld1</i> strain was only slightly lower (92%) than the control. In contrast, the sensitivity to formaldehyde pulses (up to 8mM) was significantly higher in the Δ<i>fld1</i> mutant strain and was associated with a higher maintenance energy. In addition, the intracellular flux estimation revealed a high metabolic flexibility of <i>K. phaffii</i> in response to the disrupted pathway. Our results suggest that the role of the dissimilative pathway is mainly to protect the cells from the harmful effect of formaldehyde, as they were able to compensate for the energy provided from this pathway when disrupted.

Item Type: Article
Uncontrolled Keywords: dissimilative pathway, formaldehyde dehydrogenase, Komagataella phaffii, methanol, Pichia pastoris
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Tech, Infrastructure and Environmental Directorate
Depositing User: Symplectic Admin
Date Deposited: 02 Feb 2024 11:40
Last Modified: 02 Feb 2024 11:40
DOI: 10.3390/microorganisms10071466
Open Access URL: https://doi.org/10.3390/microorganisms10071466
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3178344
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