Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework

Santos, Willians de Oliveira; de Oliveira, Rafael David; Giannari, Dafni; Barghout, Rana Ahmed; Tremblay, Alexandre; Mahadevan, Radhakrishnan; Gomez, José Gregório Cabrera; Le Roux, Galo Antonio Carrillo

doi:10.3390/pr14101659

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Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework

by

Willians de Oliveira Santos

¹

,

Rafael David de Oliveira

²,

Dafni Giannari

³

,

Rana Ahmed Barghout

³,

Alexandre Tremblay

³,

Radhakrishnan Mahadevan

³,

José Gregório Cabrera Gomez

⁴

and

Galo Antonio Carrillo Le Roux

^1,*

¹

Department of Chemical Engineering Polytechnic School, University of São Paulo, Av. Prof. Luciano Gualberto, 380, São Paulo 05508-010, Brazil

²

Department of Chemical Engineering, Norwegian University of Science and Technology (NTNU), Torgarden, NO-7491, 8900 Trondheim, Norway

³

Department of Chemical Engineering and Applied Chemistry, University of Toronto, College St., 200, Toronto, ON M5S 3E5, Canada

⁴

Institute of Biomedical Sciences, Bioproducts Laboratory, University of São Paulo, Av. Prof. Lineu Prestes, 2415, São Paulo 05508-000, Brazil

^*

Author to whom correspondence should be addressed.

Processes 2026, 14(10), 1659; https://doi.org/10.3390/pr14101659

Submission received: 23 April 2026 / Revised: 14 May 2026 / Accepted: 15 May 2026 / Published: 20 May 2026

(This article belongs to the Special Issue Modeling and Optimization for Multi-Scale Integration, 2nd Edition)

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Abstract

As the world recognizes the need for more sustainable practices, greater effort has been put into improving the economic viability of bioprocesses. Fields like metabolic engineering explore strategies to improve the production of bioproducts of industrial relevance, such as the use of alternative carbon sources. Regarding the performance assessment of a bioprocess, the product yield can be helpful, but other parameters like product titer and productivity (rate of production) are just as important. Furthermore, the highest performance may not come from a scenario with the highest yield, titer or productivity, but from a titer, rate, yield (TRY) set that maximizes profitability when the production costs are considered. Our previous work introduced the DySEEP approach, which uses an economic metric based on TRY parameters for evaluation of the potential of bioprocesses. This work expands the DySEEP program in key areas such as adding the possibility of exploring fed-batch processes and using strain design algorithms. Taking batch and fed-batch poly-3-hydroxybutyrate (PHB) production with E. coli as the case study, the scenarios that would lead to economic viability and the theoretical maximum performance for three different carbon sources, glucose, glycerol, and xylose, were identified. The results were then set in a strain design algorithm using Minimal Cut Sets (MCS) to find genetic interventions that could achieve the desired performance. The genetic interventions found with the MCS algorithm successfully led to strains that achieve the economic viability scenario, based on in silico simulations. This work illustrates how the expanded approach can be used to guide metabolic engineering strategies to improve the production of important bioproducts.

Keywords: technoeconomic analysis; flux balance analysis; Minimal Cut Sets; metabolic engineering; poly-3-hydroxybutyrate

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MDPI and ACS Style

Santos, W.d.O.; de Oliveira, R.D.; Giannari, D.; Barghout, R.A.; Tremblay, A.; Mahadevan, R.; Gomez, J.G.C.; Le Roux, G.A.C. Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework. Processes 2026, 14, 1659. https://doi.org/10.3390/pr14101659

AMA Style

Santos WdO, de Oliveira RD, Giannari D, Barghout RA, Tremblay A, Mahadevan R, Gomez JGC, Le Roux GAC. Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework. Processes. 2026; 14(10):1659. https://doi.org/10.3390/pr14101659

Chicago/Turabian Style

Santos, Willians de Oliveira, Rafael David de Oliveira, Dafni Giannari, Rana Ahmed Barghout, Alexandre Tremblay, Radhakrishnan Mahadevan, José Gregório Cabrera Gomez, and Galo Antonio Carrillo Le Roux. 2026. "Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework" Processes 14, no. 10: 1659. https://doi.org/10.3390/pr14101659

APA Style

Santos, W. d. O., de Oliveira, R. D., Giannari, D., Barghout, R. A., Tremblay, A., Mahadevan, R., Gomez, J. G. C., & Le Roux, G. A. C. (2026). Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework. Processes, 14(10), 1659. https://doi.org/10.3390/pr14101659

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Cellular- to Plant-Scale Techno-Economic and Strain Design Analysis for Batch and Fed-Batch Process with the DySEEP Framework

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