scholarly journals NMPC-Based Workflow for Simultaneous Process and Model Development Applied to a Fed-Batch Process for Recombinant C. glutamicum

Processes ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 1313
Author(s):  
Philipp Levermann ◽  
Fabian Freiberger ◽  
Uma Katha ◽  
Henning Zaun ◽  
Johannes Möller ◽  
...  

For the fast and improved development of bioprocesses, new strategies are required where both strain and process development are performed in parallel. Here, a workflow based on a Nonlinear Model Predictive Control (NMPC) algorithm is described for the model-assisted development of biotechnological processes. By using the NMPC algorithm, the process is designed with respect to a target function (product yield, biomass concentration) with a drastically decreased number of experiments. A workflow for the usage of the NMPC algorithm as a process development tool is outlined. The NMPC algorithm is capable of improving various process states, such as product yield and biomass concentration. It uses on-line and at-line data and controls and optimizes the process by model-based process extrapolation. In this study, the algorithm is applied to a Corynebacterium glutamicum process. In conclusion, the potency of the NMPC algorithm as a powerful tool for process development is demonstrated. In particular, the benefits of the system regarding the characterization and optimization of a fed-batch process are outlined. With the NMPC algorithm, process development can be run simultaneously to strain development, resulting in a shortened time to market for novel products.

2015 ◽  
Vol 4 (2) ◽  
pp. 165 ◽  
Author(s):  
Mahsa Madani Hosseini ◽  
Catherine N. Mulligan ◽  
Suzelle Barrington

<p class="emsd">In-Storage-Psychrophilic-Anaerobic-Digestion (ISPAD) is a treatment system applicable to wastewaters stored for over 100 days, such as livestock wastes and municipal sludge. The ISPAD system differs from conventional reactors by being a sequentially fed batch process operating at a temperature fluctuating with ambient. The objective of this study was to develop a mathematical model to simulate the ISPAD process, verify the value of its microbial kinetics, and to simulate the pH evolution of its content along with its methane (CH<sub>4</sub>) production. Furthermore, the values of the ISPAD microbial kinetics were compared to that of previous years to track for further acclimation to psychrophilic conditions. Simulation of ISPAD was achieved using the Simulink/Matlab software. The model was calibrated using laboratory data obtained from batch experiments using 7-year-old ISPAD inoculum, and glucose as substrate, and where glucose, VFAs and pH changes were monitored along with biogas production. The ISPAD model showed good agreement with the experimental data representing the system behaviour between 4 and 35 ºC. Although microbial activity at 4 °C was much slower than that at 18 and 35 ºC, it showed acclimation to low temperatures. Furthermore, comparison of microbial kinetic values over 3 years of field ISPAD monitoring demonstrated continued population acclimation, especially for the methanogens.</p>


2003 ◽  
Vol 83 (6) ◽  
pp. 668-680 ◽  
Author(s):  
Christopher Cannizzaro ◽  
Martin Rhiel ◽  
Ian Marison ◽  
Urs von Stockar

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0248382
Author(s):  
Emanuela Palomba ◽  
Valentina Tirelli ◽  
Elisabetta de Alteriis ◽  
Palma Parascandola ◽  
Carmine Landi ◽  
...  

The yeast Saccharomyces cerevisiae is a reference model system and one of the widely used microorganisms in many biotechnological processes. In industrial yeast applications, combined strategies aim to maximize biomass/product yield, with the fed-batch culture being one of the most frequently used. Flow cytometry (FCM) is widely applied in biotechnological processes and represents a key methodology to monitor cell population dynamics. We propose here an application of FCM in the analysis of yeast cell cycle along the time course of a typical S. cerevisiae fed-batch culture. We used two different dyes, SYTOX Green and SYBR Green, with the aim to better define each stage of cell cycle during S. cerevisiae fed-batch culture. The results provide novel insights in the use of FCM cell cycle analysis for the real-time monitoring of S. cerevisiae bioprocesses.


2010 ◽  
pp. 331-336
Author(s):  
Scott D. Storms ◽  
Jenny Y. Bang ◽  
Tom Fletcher

2012 ◽  
Vol 110 (1) ◽  
pp. 191-205 ◽  
Author(s):  
Franklin Lu ◽  
Poh Choo Toh ◽  
Iain Burnett ◽  
Feng Li ◽  
Terry Hudson ◽  
...  

2021 ◽  
Author(s):  
Massimo Sanchez ◽  
Emanuela Palomba ◽  
Valentina Tirelli ◽  
Elisabetta de Alteriis ◽  
Carmine Landi ◽  
...  

The yeast Saccharomyces cerevisiae is a reference model system and one of the widely used microorganisms in many biotechnological processes. In industrial yeast applications, combined strategies aim to maximize biomass/product yield, with the fed-batch culture being one of the most frequently used. Flow cytometry (FCM) is widely applied in biotechnological processes and represents a key methodology to monitor cell population dynamics. We propose here an application of FCM in the analysis of yeast cell cycle along the time course of a typical S. cerevisiae fed-batch culture. We used two different dyes, SYTOX Green and SYBR Green, with the aim to better define each stage of cell cycle during S. cerevisiae fed-batch culture. The results provide novel insights in the use of FCM cell cycle analysis for the real-time monitoring of S. cerevisiae bioprocesses.


Fermentation ◽  
2018 ◽  
Vol 4 (3) ◽  
pp. 79 ◽  
Author(s):  
Loïc Habegger ◽  
Kelly Rodrigues Crespo ◽  
Michal Dabros

At specific growth rates above a particular critical value, Crabtree-positive microorganisms exceed their respiratory capacity and enter diauxic growth metabolism. Excess substrate is converted reductively to an overflow metabolite, resulting in decreased biomass yield and productivity. To prevent this scenario, the cells can be cultivated in a fed-batch mode at a growth rate maintained below the critical value, µcrit. This approach entails two major challenges: accurately estimating the current specific growth rate and controlling it successfully over the course of the fermentation. In this work, the specific growth rate of S. cerevisiae and E. coli was estimated from enhanced on-line biomass concentration measurements obtained with dielectric spectroscopy and turbidity. A feedforward-feedback control scheme was implemented to maintain the specific growth rate at a setpoint below µcrit, while on-line FTIR measurements provided the early detection of the overflow metabolites. The proposed approach is in line with the principles of Bioprocess Analytical Technology (BioPAT), and provides a means to increase the productivity of Crabtree-positive microorganisms.


2019 ◽  
Vol 57 (3) ◽  
pp. 388-398 ◽  
Author(s):  
Tábita Veiga Dias Rodrigues ◽  
Thalita D. Amore ◽  
Erika Carvalho Teixeira ◽  
Janaina Fernandes de Medeiros Burkert

Carotenoids are natural pigments that can be produced through biotechnological processes. However, the costs are relatively high and can be minimized by using lower-cost substrates as alternative nutrient sources. The fed-batch fermentation is one of the techniques used to obtain a high biomass concentration and/or maximum production. Thus, the aim of this work is to produce carotenoids in batch and fed-batch fermentation with the yeast Rhodotorula mucilaginosa CCT 7688 using agroindustrial byproducts in the culture medium. Carotenoid production was increased using experimental designs, which modified the concentration of the agroindustrial medium. In batch production the highest concentrations of total carotenoids (1248.5 μg/L) and biomass (7.9 g/L) were obtained in the medium containing 70 g/L sugar cane molasses and 3.4 g/L corn steep liquor at 25 °C and 180 rpm in 168 h, demonstrating an increase of 17 % when compared to the standard yeast malt medium (1200 μg/L). In the fed-batch production, different feeding strategies were tested with 30 g/L sugar cane molasses and 6.5 g/L corn steep liquor, reaching a total carotenoid production of 3726 μg/L and biomass concentration of 16 g/L. Therefore, the strategy of the fed-batch process resulted in an increase in the carotenoid production of approx. 400 % compared to that in the batch process (740.3 μg/L). Thus, the R. mucilaginosa strain has the potential to produce carotenoids in agroindustrial medium.


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