期刊
PROCESSES
卷 8, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pr8060657
关键词
metabolic modelling; poly(3-hydroxybutyric acid); flux balance analysis; bioprocess; constraint-based stoichiometric modelling; pseudo-steady state; thermodynamics; data-driven approach
资金
- University of Manchester
- EPSRC [EP/S01778X/1] Funding Source: UKRI
Cupriavidus necator DSM 545 can utilise glycerol to synthesise poly(3-hydroxybutyric acid) under unbalanced growth conditions, i.e., nitrogen limitation. To improve poly(3-hydroxybutyric acid) (PHB) batch production by C. necator through model-guided bioprocessing or genetic engineering, insights into the dynamic effect of the fermentation conditions on cell metabolism are crucial. In this work, we have used dynamic flux balance analysis (DFBA), a constrained-based stoichiometric modelling approach, to study the metabolic change associated with PHB synthesis during batch cultivation. The model employs the 'minimisation of all fluxes' as cellular objectives and measured extracellular fluxes as additional constraints. The mass balance constraints are further adjusted based on thermodynamic considerations. The resultant flux distribution profiles characterise the evolution of metabolic states due to adaptation to dynamic extracellular conditions and provide further insights towards improvements that can be implemented to enhance PHB productivity.
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