{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:28:08Z","timestamp":1789705688100,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)","award":["1191196"],"award-info":[{"award-number":["1191196"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)","award":["ACT210068"],"award-info":[{"award-number":["ACT210068"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)","award":["SUB\/2019\/435787"],"award-info":[{"award-number":["SUB\/2019\/435787"]}]},{"name":"Wallonie-Bruxelles International through the Cooperation bilateral Belgique-Chili project","award":["1191196"],"award-info":[{"award-number":["1191196"]}]},{"name":"Wallonie-Bruxelles International through the Cooperation bilateral Belgique-Chili project","award":["ACT210068"],"award-info":[{"award-number":["ACT210068"]}]},{"name":"Wallonie-Bruxelles International through the Cooperation bilateral Belgique-Chili project","award":["SUB\/2019\/435787"],"award-info":[{"award-number":["SUB\/2019\/435787"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Komagataella phaffii (aka Pichia pastoris) 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 CO2 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 (\u0394fld1) and used flux analysis to evaluate the metabolic impact of this disrupted pathway. Unexpectedly, we found that the specific growth rate of the \u0394fld1 strain was only slightly lower (92%) than the control. In contrast, the sensitivity to formaldehyde pulses (up to 8mM) was significantly higher in the \u0394fld1 mutant strain and was associated with a higher maintenance energy. In addition, the intracellular flux estimation revealed a high metabolic flexibility of K. phaffii 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.<\/jats:p>","DOI":"10.3390\/microorganisms10071466","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T03:34:40Z","timestamp":1658374480000},"page":"1466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Role of Dissimilative Pathway of Komagataella phaffii (Pichia pastoris): Formaldehyde Toxicity and Energy Metabolism"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-0023","authenticated-orcid":false,"given":"Julio","family":"Berrios","sequence":"first","affiliation":[{"name":"School of Biochemical Engineering, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Av. Brasil 2085, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-6417","authenticated-orcid":false,"given":"Chrispian W.","family":"Theron","sequence":"additional","affiliation":[{"name":"GeneMill, Institute of Systems, Molecular and Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Steels","sequence":"additional","affiliation":[{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Li\u00e8ge, Av. de la Facult\u00e9 2B, 5030 Gembloux, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-4389","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Ponce","sequence":"additional","affiliation":[{"name":"School of Biochemical Engineering, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Av. Brasil 2085, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Velastegui","sequence":"additional","affiliation":[{"name":"School of Biochemical Engineering, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Av. Brasil 2085, Valpara\u00edso 2340000, Chile"},{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Li\u00e8ge, Av. de la Facult\u00e9 2B, 5030 Gembloux, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-2993","authenticated-orcid":false,"given":"Cristina","family":"Bustos","sequence":"additional","affiliation":[{"name":"School of Biochemical Engineering, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Av. Brasil 2085, Valpara\u00edso 2340000, Chile"},{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Li\u00e8ge, Av. de la Facult\u00e9 2B, 5030 Gembloux, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Altamirano","sequence":"additional","affiliation":[{"name":"School of Biochemical Engineering, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Av. Brasil 2085, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-5833","authenticated-orcid":false,"given":"Patrick","family":"Fickers","sequence":"additional","affiliation":[{"name":"Microbial Processes and Interactions, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Li\u00e8ge, Av. de la Facult\u00e9 2B, 5030 Gembloux, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bustos, C., Quezada, J., Veas, R., Altamirano, C., Braun-Galleani, S., Fickers, P., and Berrios, J. (2022). Advances in Cell Engineering of the Komagataella phaffii Platform for Recombinant Protein Production. 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