Predictive dynamic control accurately maps the design space for 2,3-butanediol production

Author(s)
Mathias Gotsmy, Anna Erian, Hans Marx, Stefan Pflügl, Jürgen Zanghellini
Abstract

2,3-Butanediol is a valuable raw material for many industries. Compared to its classical production from petroleum, novel fermentation-based manufacturing is an ecologically superior alternative. To be also economically feasible, the production bioprocesses need to be well optimized. Here, we adapted and applied a novel process optimization algorithm, dynamic control flux-balance analysis (dcFBA), for 2,3-butanediol production in E. coli. First, we performed two-stage fed-batch process simulations with varying process lengths. There, we found that the solution space can be separated into a proportionality and a trade-off region. With the information of the simulations we were able to design close-to-optimal production processes for maximizing titer and productivity, respectively. Experimental validations resulted in a titer of [Formula presented] and a productivity of [Formula presented]. Subsequently, we optimized a continuous two-reactor process setup for 2,3-butanediol productivity. We found that in this mode, it is possible to increase the productivity more than threefold with minor impact on the titer and yield. Biotechnological process optimization is cumbersome, therefore, many processes are run in suboptimal conditions. We are confident that the method presented here, will help to make many biotechnological productions economically feasible in the future.

Organisation(s)
Department of Analytical Chemistry
External organisation(s)
acib – Austrian Centre of Industrial Biotechnology, University of Natural Resources and Life Sciences, Technische Universität Wien
Journal
Computational and Structural Biotechnology Journal
Volume
23
Pages
3850-3858
No. of pages
9
ISSN
2001-0370
DOI
https://doi.org/10.1016/j.csbj.2024.10.016
Publication date
12-2024
Peer reviewed
Yes
Austrian Fields of Science 2012
104027 Computational chemistry
Keywords
ASJC Scopus subject areas
Biotechnology, Biophysics, Structural Biology, Biochemistry, Genetics, Computer Science Applications
Portal url
https://ucrisportal.univie.ac.at/en/publications/454fe009-4f5c-4b36-88ea-b68fef5cba30