A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis
Recent advances in the availability and applicability of genetic tools for non-conventional yeasts have raised high hopes regarding the industrial applications of such yeasts; however, quantitative physiological data on these yeasts, including intracellular flux distributions, are scarce and have ra...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-12-01
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| Series: | Metabolic Engineering Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214030117300068 |
| _version_ | 1818541747925417984 |
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| author | Mathias Lehnen Birgitta E. Ebert Lars M. Blank |
| author_facet | Mathias Lehnen Birgitta E. Ebert Lars M. Blank |
| author_sort | Mathias Lehnen |
| collection | DOAJ |
| description | Recent advances in the availability and applicability of genetic tools for non-conventional yeasts have raised high hopes regarding the industrial applications of such yeasts; however, quantitative physiological data on these yeasts, including intracellular flux distributions, are scarce and have rarely aided in the development of novel yeast applications. The compartmentation of eukaryotic cells adds to model complexity. Model constraints are ideally based on biochemical evidence, which is rarely available for non-conventional yeast and eukaryotic cells. A small-scale model for 13C-based metabolic flux analysis of central yeast carbon metabolism was developed that is universally valid and does not depend on localization information regarding amino acid anabolism. The variable compartmental origin of traced metabolites is a feature that allows application of the model to yeasts with uncertain genomic and transcriptional backgrounds. The presented test case includes the baker's yeast Saccharomyces cerevisiae and the methylotrophic yeast Hansenula polymorpha. Highly similar flux solutions were computed using either a model with undefined pathway localization or a model with constraints based on curated (S. cerevisiae) or computationally predicted (H. polymorpha) localization information, while false solutions were found with incorrect localization constraints. These results indicate a potentially adverse effect of universally assuming Saccharomyces-like constraints on amino acid biosynthesis for non-conventional yeasts and verify the validity of neglecting compartmentation constraints using a small-scale metabolic model. The model was specifically designed to investigate the intracellular metabolism of wild-type yeasts under various growth conditions but is also expected to be useful for computing fluxes of other eukaryotic cells. |
| first_indexed | 2024-12-11T22:13:15Z |
| format | Article |
| id | doaj.art-f3b9bbf8f4bf42868f68a4eb405ca2ad |
| institution | Directory Open Access Journal |
| issn | 2214-0301 |
| language | English |
| last_indexed | 2024-12-11T22:13:15Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolic Engineering Communications |
| spelling | doaj.art-f3b9bbf8f4bf42868f68a4eb405ca2ad2022-12-22T00:48:42ZengElsevierMetabolic Engineering Communications2214-03012017-12-015C344410.1016/j.meteno.2017.07.001A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysisMathias LehnenBirgitta E. EbertLars M. BlankRecent advances in the availability and applicability of genetic tools for non-conventional yeasts have raised high hopes regarding the industrial applications of such yeasts; however, quantitative physiological data on these yeasts, including intracellular flux distributions, are scarce and have rarely aided in the development of novel yeast applications. The compartmentation of eukaryotic cells adds to model complexity. Model constraints are ideally based on biochemical evidence, which is rarely available for non-conventional yeast and eukaryotic cells. A small-scale model for 13C-based metabolic flux analysis of central yeast carbon metabolism was developed that is universally valid and does not depend on localization information regarding amino acid anabolism. The variable compartmental origin of traced metabolites is a feature that allows application of the model to yeasts with uncertain genomic and transcriptional backgrounds. The presented test case includes the baker's yeast Saccharomyces cerevisiae and the methylotrophic yeast Hansenula polymorpha. Highly similar flux solutions were computed using either a model with undefined pathway localization or a model with constraints based on curated (S. cerevisiae) or computationally predicted (H. polymorpha) localization information, while false solutions were found with incorrect localization constraints. These results indicate a potentially adverse effect of universally assuming Saccharomyces-like constraints on amino acid biosynthesis for non-conventional yeasts and verify the validity of neglecting compartmentation constraints using a small-scale metabolic model. The model was specifically designed to investigate the intracellular metabolism of wild-type yeasts under various growth conditions but is also expected to be useful for computing fluxes of other eukaryotic cells.http://www.sciencedirect.com/science/article/pii/S221403011730006813C-metabolic flux analysisEukaryotesCompartmented metabolismNon-conventional yeastS. cerevisiaeH. polymorpha |
| spellingShingle | Mathias Lehnen Birgitta E. Ebert Lars M. Blank A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis Metabolic Engineering Communications 13C-metabolic flux analysis Eukaryotes Compartmented metabolism Non-conventional yeast S. cerevisiae H. polymorpha |
| title | A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| title_full | A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| title_fullStr | A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| title_full_unstemmed | A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| title_short | A comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| title_sort | comprehensive evaluation of constraining amino acid biosynthesis in compartmented models for metabolic flux analysis |
| topic | 13C-metabolic flux analysis Eukaryotes Compartmented metabolism Non-conventional yeast S. cerevisiae H. polymorpha |
| url | http://www.sciencedirect.com/science/article/pii/S2214030117300068 |
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