Dynamic Metabolic Flux Analysis Demonstrated on Cultures Where the Limiting Substrate Is Changed from Carbon to Nitrogen and Vice Versa
The main requirement for metabolic flux analysis (MFA) is that the cells are in a pseudo-steady state, that there is no accumulation or depletion of intracellular metabolites. In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the c...
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| Veröffentlicht in: | BioMed research international 2010-01, Vol.2010 (2010), p.1-19 |
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| creator | Beauprez, Joeri Lequeux, Gaspard Maertens, Jo Van Horen, Ellen Soetaert, Wim Vandamme, Erick Vanrolleghem, Peter A. |
| description | The main requirement for metabolic flux analysis (MFA) is that the cells are in a pseudo-steady state, that there is no accumulation or depletion of intracellular metabolites. In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the concept of dynamic MFA and extends MFA so that it is applicable to transient cultures. Time series of concentration measurements are transformed into flux values. This transformation involves differentiation, which typically increases the noisiness of the data. Therefore, a noise-reducing step is needed. In this work, polynomial smoothing was used. As a test case, dynamic MFA is applied on Escherichia coli cultivations shifting from carbon limitation to nitrogen limitation and vice versa. After switching the limiting substrate from N to C, a lag phase was observed accompanied with an increase in maintenance energy requirement. This lag phase did not occur in the C- to N-limitation case. |
| doi_str_mv | 10.1155/2010/621645 |
| format | Article |
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In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the concept of dynamic MFA and extends MFA so that it is applicable to transient cultures. Time series of concentration measurements are transformed into flux values. This transformation involves differentiation, which typically increases the noisiness of the data. Therefore, a noise-reducing step is needed. In this work, polynomial smoothing was used. As a test case, dynamic MFA is applied on Escherichia coli cultivations shifting from carbon limitation to nitrogen limitation and vice versa. After switching the limiting substrate from N to C, a lag phase was observed accompanied with an increase in maintenance energy requirement. This lag phase did not occur in the C- to N-limitation case.</description><identifier>ISSN: 1110-7243</identifier><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 1110-7251</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2010/621645</identifier><identifier>PMID: 20827435</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Adenosine Triphosphate - metabolism ; Applied mathematics ; Bacteria ; Biomass ; Biomedical research ; Carbon ; Carbon - metabolism ; Carbon - pharmacology ; Carbon Dioxide - metabolism ; Cell Culture Techniques - methods ; Chemical properties ; Constraining ; Culture ; Depletion ; Dynamics ; E coli ; Escherichia coli ; Escherichia coli - cytology ; Escherichia coli - drug effects ; Escherichia coli - growth & development ; Escherichia coli - metabolism ; Flux ; Hydrolysis - drug effects ; Maintenance ; Metabolic Networks and Pathways - drug effects ; Metabolism ; Metabolites ; Nitrogen ; Nitrogen - pharmacology ; Noise ; Oxygen Consumption - drug effects ; Process controls ; Substrate Specificity - drug effects ; Substrates (Biochemistry) ; Time Factors ; Time series ; Transformations ; Vices</subject><ispartof>BioMed research international, 2010-01, Vol.2010 (2010), p.1-19</ispartof><rights>Copyright © 2010 Gaspard Lequeux et al.</rights><rights>COPYRIGHT 2010 John Wiley & Sons, Inc.</rights><rights>Copyright © 2010 Gaspard Lequeux et al. Gaspard Lequeux et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2010 Gaspard Lequeux et al. 2010 Copyright © 2010 Gaspard Lequeux et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c597t-59e46ac73e864bf2d42bab60021df4af67a90929b92e2666f29119d550bfa9083</citedby><cites>FETCH-LOGICAL-c597t-59e46ac73e864bf2d42bab60021df4af67a90929b92e2666f29119d550bfa9083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934775/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934775/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20827435$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Antoniewicz, Maciek</contributor><creatorcontrib>Beauprez, Joeri</creatorcontrib><creatorcontrib>Lequeux, Gaspard</creatorcontrib><creatorcontrib>Maertens, Jo</creatorcontrib><creatorcontrib>Van Horen, Ellen</creatorcontrib><creatorcontrib>Soetaert, Wim</creatorcontrib><creatorcontrib>Vandamme, Erick</creatorcontrib><creatorcontrib>Vanrolleghem, Peter A.</creatorcontrib><title>Dynamic Metabolic Flux Analysis Demonstrated on Cultures Where the Limiting Substrate Is Changed from Carbon to Nitrogen and Vice Versa</title><title>BioMed research international</title><addtitle>J Biomed Biotechnol</addtitle><description>The main requirement for metabolic flux analysis (MFA) is that the cells are in a pseudo-steady state, that there is no accumulation or depletion of intracellular metabolites. In the past, the applications of MFA were limited to the analysis of continuous cultures. This contribution introduces the concept of dynamic MFA and extends MFA so that it is applicable to transient cultures. Time series of concentration measurements are transformed into flux values. This transformation involves differentiation, which typically increases the noisiness of the data. Therefore, a noise-reducing step is needed. In this work, polynomial smoothing was used. As a test case, dynamic MFA is applied on Escherichia coli cultivations shifting from carbon limitation to nitrogen limitation and vice versa. After switching the limiting substrate from N to C, a lag phase was observed accompanied with an increase in maintenance energy requirement. This lag phase did not occur in the C- to N-limitation case.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Applied mathematics</subject><subject>Bacteria</subject><subject>Biomass</subject><subject>Biomedical research</subject><subject>Carbon</subject><subject>Carbon - metabolism</subject><subject>Carbon - pharmacology</subject><subject>Carbon Dioxide - metabolism</subject><subject>Cell Culture Techniques - methods</subject><subject>Chemical properties</subject><subject>Constraining</subject><subject>Culture</subject><subject>Depletion</subject><subject>Dynamics</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Escherichia coli - cytology</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli - growth & development</subject><subject>Escherichia coli - metabolism</subject><subject>Flux</subject><subject>Hydrolysis - drug effects</subject><subject>Maintenance</subject><subject>Metabolic Networks and Pathways - 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| subjects | Adenosine Triphosphate - metabolism Applied mathematics Bacteria Biomass Biomedical research Carbon Carbon - metabolism Carbon - pharmacology Carbon Dioxide - metabolism Cell Culture Techniques - methods Chemical properties Constraining Culture Depletion Dynamics E coli Escherichia coli Escherichia coli - cytology Escherichia coli - drug effects Escherichia coli - growth & development Escherichia coli - metabolism Flux Hydrolysis - drug effects Maintenance Metabolic Networks and Pathways - drug effects Metabolism Metabolites Nitrogen Nitrogen - pharmacology Noise Oxygen Consumption - drug effects Process controls Substrate Specificity - drug effects Substrates (Biochemistry) Time Factors Time series Transformations Vices |
| title | Dynamic Metabolic Flux Analysis Demonstrated on Cultures Where the Limiting Substrate Is Changed from Carbon to Nitrogen and Vice Versa |
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