Optimization of nutrient utilization efficiency and productivity for algal cultures under light and dark cycles using genome-scale model process control.

Chien-Ting Li, Richard Eng, Cristal Zuniga, Kai-Wen Huang, Yiqun Chen, Karsten Zengler, Michael J Betenbaugh

Journal: NPJ systems biology and applications 2023;9(1):7

PMID: 36922521

Abstract

Algal cultivations are strongly influenced by light and dark cycles. In this study, genome-scale metabolic models were applied to optimize nutrient supply during alternating light and dark cycles of Chlorella vulgaris. This approach lowered the glucose requirement by 75% and nitrate requirement by 23%, respectively, while maintaining high final biomass densities that were more than 80% of glucose-fed heterotrophic culture. Furthermore, by strictly controlling glucose feeding during the alternating cycles based on model-input, yields of biomass, lutein, and fatty acids per gram of glucose were more than threefold higher with cycling compared to heterotrophic cultivation. Next, the model was incorporated into open-loop and closed-loop control systems and compared with traditional fed-batch systems. Closed-loop systems which incorporated a feed-optimizing algorithm increased biomass yield on glucose more than twofold compared to standard fed-batch cultures for cycling cultures. Finally, the performance was compared to conventional proportional-integral-derivative (PID) controllers. Both simulation and experimental results exhibited superior performance for genome-scale model process control (GMPC) compared to traditional PID systems, reducing the overall measured value and setpoint error by 80% over 8 h. Overall, this approach provides researchers with the capability to enhance nutrient utilization and productivity of cell factories systematically by combining genome-scale models and controllers into an integrated platform with superior performance to conventional fed-batch and PID methodologies.

© 2023. The Author(s).

Address: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0760, USA.; Department of Biology, San Diego State University, San Diego, USA.; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0412, USA.; Center for Microbiome Innovation, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0436, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA. [email protected].
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