Espinel‐Ríos, Sebastián ; Morabito, Bruno ; Pohlodek, Johannes ; Bettenbrock, Katja ; Klamt, Steffen ; Findeisen, Rolf (2024)
Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics.
In: Biotechnology and Bioengineering, 2024, 121 (1)
doi: 10.26083/tuprints-00027245
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Biotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes extracellular process elements such as the bioreactor design and mode of operation, medium formulation, culture conditions, feeding rates, and so on. However, these elements are frequently insufficient for achieving optimal process performance or precise product composition. One can use metabolic and genetic engineering methods for optimization at the intracellular level. Nevertheless, those are often of static nature, failing when applied to dynamic processes or if disturbances occur. Furthermore, many bioprocesses are optimized empirically and implemented with little‐to‐no feedback control to counteract disturbances. The concept of cybergenetics has opened new possibilities to optimize bioprocesses by enabling online modulation of the gene expression of metabolism‐relevant proteins via external inputs (e.g., light intensity in optogenetics). Here, we fuse cybergenetics with model‐based optimization and predictive control for optimizing dynamic bioprocesses. To do so, we propose to use dynamic constraint‐based models that integrate the dynamics of metabolic reactions, resource allocation, and inducible gene expression. We formulate a model‐based optimal control problem to find the optimal process inputs. Furthermore, we propose using model predictive control to address uncertainties via online feedback. We focus on fed‐batch processes, where the substrate feeding rate is an additional optimization variable. As a simulation example, we show the optogenetic control of the ATPase enzyme complex for dynamic modulation of enforced ATP wasting to adjust product yield and productivity.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Espinel‐Ríos, Sebastián ; Morabito, Bruno ; Pohlodek, Johannes ; Bettenbrock, Katja ; Klamt, Steffen ; Findeisen, Rolf |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics |
| Sprache: | Englisch |
| Publikationsjahr: | 21 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | Januar 2024 |
| Ort der Erstveröffentlichung: | New York |
| Verlag: | Wiley |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Biotechnology and Bioengineering |
| Jahrgang/Volume einer Zeitschrift: | 121 |
| (Heft-)Nummer: | 1 |
| DOI: | 10.26083/tuprints-00027245 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27245 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Biotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes extracellular process elements such as the bioreactor design and mode of operation, medium formulation, culture conditions, feeding rates, and so on. However, these elements are frequently insufficient for achieving optimal process performance or precise product composition. One can use metabolic and genetic engineering methods for optimization at the intracellular level. Nevertheless, those are often of static nature, failing when applied to dynamic processes or if disturbances occur. Furthermore, many bioprocesses are optimized empirically and implemented with little‐to‐no feedback control to counteract disturbances. The concept of cybergenetics has opened new possibilities to optimize bioprocesses by enabling online modulation of the gene expression of metabolism‐relevant proteins via external inputs (e.g., light intensity in optogenetics). Here, we fuse cybergenetics with model‐based optimization and predictive control for optimizing dynamic bioprocesses. To do so, we propose to use dynamic constraint‐based models that integrate the dynamics of metabolic reactions, resource allocation, and inducible gene expression. We formulate a model‐based optimal control problem to find the optimal process inputs. Furthermore, we propose using model predictive control to address uncertainties via online feedback. We focus on fed‐batch processes, where the substrate feeding rate is an additional optimization variable. As a simulation example, we show the optogenetic control of the ATPase enzyme complex for dynamic modulation of enforced ATP wasting to adjust product yield and productivity. |
| Freie Schlagworte: | constraint‐based modeling, dynamic metabolic control, metabolic cybergenetics, model predictive control, optogenetics, state estimation |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-272452 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 621.3 Elektrotechnik, Elektronik |
| Fachbereich(e)/-gebiet(e): | 18 Fachbereich Elektrotechnik und Informationstechnik 18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Automatisierungstechnik und Mechatronik 18 Fachbereich Elektrotechnik und Informationstechnik > Institut für Automatisierungstechnik und Mechatronik > Control and Cyber-Physical Systems (CCPS) |
| Hinterlegungsdatum: | 21 Mai 2024 13:48 |
| Letzte Änderung: | 23 Mai 2024 13:51 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics. (deposited 21 Mai 2024 13:48) [Gegenwärtig angezeigt]
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