Simultaneous design of fermentation and microbe

AIChE Journal, vol. 70

Abstract

Abstract Constraint‐based optimization of microbial strains and model‐based bioprocess design have been used extensively to enhance yields in biotechnological processes. However, strain and process optimization are usually carried out in sequential steps, causing underperformance of the biotechnological process when scaling up to industrial fermentation conditions. Herein, we propose the optimization formulation SimulKnock that combines the optimization of a fermentation process with metabolic network design in a bilevel optimization program. The upper level maximizes space‐time yield and includes mass balances of a continuous fermentation, while the lower level is based on flux balance analysis. SimulKnock predicts optimal gene deletions and finds the optimal trade‐off between growth rate and product yield. Results of a case study with a genome‐scale metabolic model of Escherichia coli indicate higher space‐time yields than a sequential approach using OptKnock for almost all target products considered. By leveraging SimulKnock, we reduce the gap between strain and process optimization.

Authors 5

1. Anita L. Ziegler Aachen Process Systems Engineering (AVT.SVT)

   RWTH Aachen University

   Affiliation as printed

   Process Systems Engineering (AVT.SVT) RWTH Aachen University Aachen Germany

   Process Systems Engineering (AVT.SVT), RWTH Aachen University, Aachen, Germany

2. Ashutosh Manchanda Aachen Process Systems Engineering (AVT.SVT)

   RWTH Aachen University

   Affiliation as printed

   Process Systems Engineering (AVT.SVT) RWTH Aachen University Aachen Germany

   Process Systems Engineering (AVT.SVT), RWTH Aachen University, Aachen, Germany

3. Marc‐Daniel Stumm Aachen Process Systems Engineering (AVT.SVT)

   RWTH Aachen University

   Affiliation as printed

   Process Systems Engineering (AVT.SVT) RWTH Aachen University Aachen Germany

   Process Systems Engineering (AVT.SVT), RWTH Aachen University, Aachen, Germany

4. Lars M. Blank Aachen Institute of Applied Microbiology

   RWTH Aachen University

   Affiliation as printed

   Institute of Applied Microbiology (iAMB), Aachen Biology and Biotechnology (ABBt) RWTH Aachen University Aachen Germany

   Institute of Applied Microbiology (iAMB), Aachen Biology and Biotechnology (ABBt), RWTH Aachen University, Aachen, Germany

5. Alexander Mitsos corresponding Aachen Process Systems Engineering (AVT.SVT)

   Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Institute of Energy and Climate Research, Energy Systems Engineering (IEK‐10) Forschungszentrum Jülich GmbH Jülich Germany

   JARA‐ENERGY Aachen Germany

   Process Systems Engineering (AVT.SVT) RWTH Aachen University Aachen Germany

   JARA-ENERGY, Aachen, Germany

   Process Systems Engineering (AVT.SVT), RWTH Aachen University, Aachen, Germany