‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database
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...
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| Published in | Microbial cell factories Vol. 23; no. 1; pp. 1 - 20 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central Ltd
18.01.2024
BioMed Central BMC |
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| Online Access | Get full text |
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| Abstract | 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. 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. All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. |
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| AbstractList | 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. 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. All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. 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. 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. All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. BackgroundIn 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.ResultsTechnically, 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.ConclusionsAll potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. Background 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 ( Conclusions All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. Keywords: Yeast, Transcription factors, Stress resistance, Protein production, Global metabolic engineering, Yarrowia cultivation protocol 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.BACKGROUNDIn 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.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.RESULTSTechnically, 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.All potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest.CONCLUSIONSAll potential users are invited to browse YaliFunTome in the search for homologous TFs and the TF-driven phenotypes of interest. Abstract Background 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. |
| ArticleNumber | 26 |
| Audience | Academic |
| Author | Gorczyca, Maria Białas, Wojciech Celińska, Ewelina Nicaud, Jean-Marc |
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| Keywords | Transcription factors Yeast Protein production Stress resistance Global metabolic engineering Yarrowia cultivation protocol |
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| SubjectTerms | Analysis Carbon Design of experiments DNA binding proteins Engineering Experimental design Genomes Genotype & phenotype Global metabolic engineering Glycerol Health aspects Identification and classification Life Sciences Mathematical models Medicinal plants Metabolism Metabolites Nitrogen Oxidative stress Phenotypes Protein biosynthesis Protein production Protein synthesis Proteins Reporters RNA polymerase Strains (organisms) Stress resistance Transcription factors Yarrow Yarrowia cultivation protocol Yarrowia lipolytica Yeast |
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| Title | ‘Mother(Nature) knows best’ – hijacking nature-designed transcriptional programs for enhancing stress resistance and protein production in Yarrowia lipolytica; presentation of YaliFunTome database |
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