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‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database

cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0002-6095-3167
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0001-8372-8459
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cris.virtualsource.author-orcidd580fec6-bbe3-4b0a-bc14-1d11cdac2fb6
cris.virtualsource.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtualsource.author-orcid6f5a4155-2edb-48cf-b362-f3180e151169
dc.abstract.enBackground: In the era of rationally designed synthetic biology, heterologous metabolites production, and other counter-nature engineering of cellular metabolism, we took a step back and recalled that ‘Mother(-Nature) knows best’. While still aiming at synthetic, non-natural outcomes of generating an ‘over-production phenotype’ we dug into the pre-designed transcriptional programs evolved in our host organism—Yarrowia lipolytica, hoping that some of these fine-tuned orchestrated programs could be hijacked and used. Having an interest in the practical outcomes of the research, we targeted industrially-relevant functionalities—stress resistance and enhanced synthesis of proteins, and gauged them over extensive experimental design’s completion. Results: Technically, the problem was addressed by screening a broad library of over 120 Y. lipolytica strains under 72 combinations of variables through a carefully pre-optimized high-throughput cultivation protocol, which enabled actual phenotype development. The abundance of the transcription program elicitors—transcription factors (TFs), was secured by their overexpression, while challenging the strains with the multitude of conditions was inflicted to impact their activation stratus. The data were subjected to mathematical modeling to increase their informativeness. The amount of the gathered data prompted us to present them in the form of a searchable catalog – the YaliFunTome database (https://sparrow.up.poznan.pl/tsdatabase/)—to facilitate the withdrawal of biological sense from numerical data. We succeeded in the identification of TFs that act as omni-boosters of protein synthesis, enhance resistance to limited oxygen availability, and improve protein synthesis capacity under inorganic nitrogen provision. Conclusions: All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest.
dc.affiliationWydział Nauk o Żywności i Żywieniu
dc.affiliation.instituteKatedra Biotechnologii i Mikrobiologii Żywności
dc.contributor.authorGorczyca, Maria
dc.contributor.authorBiałas, Wojciech
dc.contributor.authorNicaud, Jean-Marc
dc.contributor.authorCelińska, Ewelina
dc.date.access2025-07-30
dc.date.accessioned2025-07-30T10:47:26Z
dc.date.available2025-07-30T10:47:26Z
dc.date.copyright2024-01-18
dc.date.issued2024
dc.description.abstract<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>In the era of rationally designed synthetic biology, heterologous metabolites production, and other counter-nature engineering of cellular metabolism, we took a step back and recalled that ‘Mother(-Nature) knows best’. While still aiming at synthetic, non-natural outcomes of generating an ‘over-production phenotype’ we dug into the pre-designed transcriptional programs evolved in our host organism—<jats:italic>Yarrowia lipolytica</jats:italic>, hoping that some of these fine-tuned orchestrated programs could be hijacked and used. Having an interest in the practical outcomes of the research, we targeted industrially-relevant functionalities—stress resistance and enhanced synthesis of proteins, and gauged them over extensive experimental design’s completion.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Technically, the problem was addressed by screening a broad library of over 120 <jats:italic>Y. lipolytica</jats:italic> strains under 72 combinations of variables through a carefully pre-optimized high-throughput cultivation protocol, which enabled actual phenotype development. The abundance of the transcription program elicitors—transcription factors (TFs), was secured by their overexpression, while challenging the strains with the multitude of conditions was inflicted to impact their activation stratus. The data were subjected to mathematical modeling to increase their informativeness.</jats:p> <jats:p>The amount of the gathered data prompted us to present them in the form of a searchable catalog – the YaliFunTome database (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://sparrow.up.poznan.pl/tsdatabase/">https://sparrow.up.poznan.pl/tsdatabase/</jats:ext-link>)—to facilitate the withdrawal of biological sense from numerical data. We succeeded in the identification of TFs that act as omni-boosters of protein synthesis, enhance resistance to limited oxygen availability, and improve protein synthesis capacity under inorganic nitrogen provision.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest.</jats:p> </jats:sec>
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financeother
dc.description.financecost10580,00
dc.description.if4,9
dc.description.points100
dc.description.versionfinal_published
dc.description.volume23
dc.identifier.doi10.1186/s12934-023-02285-x
dc.identifier.issn1475-2859
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/4026
dc.identifier.weblinkhttps://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-023-02285-x
dc.languageen
dc.language.isoen
dc.relation.ispartofMicrobial Cell Factories
dc.relation.pagesart. 26
dc.relation.projectCzynniki transkrypcyjne jako narzędzia masowego działania w ulepszaniu cech przemysłowych u drożdży
dc.rightsCC-BY
dc.sciencecloudsend
dc.share.typeOPEN_JOURNAL
dc.subject.entranscription factors
dc.subject.enstress resistance
dc.subject.enprotein production
dc.subject.englobal metabolic engineering
dc.subject.enYarrowia cultivation protocol
dc.subject.enyeast
dc.title‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.volume23