On-line optimization of recombinant product in a fed-batch bioreactor.

Biotechnol Prog

Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716, USA.

Published: March 2004

In this paper, an efficient scheme for on-line optimization of a recombinant product in a fed-batch bioreactor is presented. This scheme is based on the parametrization of the system states and the elimination of a subset of the dynamic equations in the mathematical model of the fed-batch bioreactor. The fed-batch bioreactor considered here involves the production of chloramphenicol acetyltransferase (CAT) in a genetically modified E. coli. The optimal inducer and the glucose feed rates are obtained using the proposed optimization approach. This approach is compared with the traditional optimization approach, where all the states and the manipulated variables are parametrized. The approach presented in this paper results in a 5-fold improvement in the computational time for the recombinant product optimization. The optimization technique is employed in an on-line optimization scheme, when parametric drift and a disturbance in the manipulated variable is present. Feedback from the process is introduced through resetting the initial conditions of the model and through an observer for estimating the time varying parameter. The simulation results indicated improvement in the amount of product formed, when the optimal profile is regenerated during the course of the batch.

Download full-text PDF

Source
http://dx.doi.org/10.1021/bp025546zDOI Listing

Publication Analysis

Top Keywords

fed-batch bioreactor
16
on-line optimization
12
recombinant product
12
optimization recombinant
8
product fed-batch
8
optimization approach
8
optimization
6
product
4
fed-batch
4
bioreactor
4

Similar Publications

Recombinant Production of Bovine α-Casein in Genome-Reduced Strain IIG-Bs-20-5-1.

Microorganisms

January 2025

Institute of Food Science and Biotechnology, Department of Bioprocess Engineering, University of Hohenheim, Fruwirthstraße 12, 70599 Stuttgart, Germany.

Background: Cow's milk represents an important protein source. Here, especially casein proteins are important components, which might be a promising source of alternative protein production by microbial expression systems. Nevertheless, caseins are difficult-to-produce proteins, making heterologous production challenging.

View Article and Find Full Text PDF

Recent years, intensified fed-batch culture with ultra-high seeding density (uHSD-IFB) is coming to the forefront of manufacturers' choice for its enhanced productivity. However, the effects of seed cell physiological state and aeration strategies on these processes remain underexplored due to the ultra-high seeding density. Currently, the pre-production seeding inoculum (N-1) crucial for the uHSD-IFB cultures relies heavily upon case-by-case empirical experiences.

View Article and Find Full Text PDF

Chinese hamster ovary (CHO) cells are widely used to produce recombinant proteins, including monoclonal antibodies (mAbs), through various process modes. While fed-batch (FB) processes have been the standard, a shift toward high-density perfusion processes is being driven by increased productivity, flexible facility footprints, and lower costs. Ensuring the clearance of process-related impurities, such as host cell proteins (HCPs), is crucial in biologics manufacturing.

View Article and Find Full Text PDF

p-Coumaric acid (p-CA), an invaluable phytochemical, has novel bioactivities, including antiproliferative, anxiolytic, and neuroprotective effects, and is the main precursor of various flavonoids, such as caffeic acid, naringenin, and resveratrol. Herein, we report the engineering of Escherichia coli for de novo production of p-CA via the PAL-C4H pathway. As the base strain, we used the E.

View Article and Find Full Text PDF

Construction of isopentenol utilization pathway and artificial multifunctional enzyme for miltiradiene synthesis in Saccharomyces cerevisiae.

Bioresour Technol

January 2025

School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China; Frontiers Science Center for Synthetic Biology, Tianjin University, Tianjin, PR China; Key Laboratory of System Bioengineering (Tianjin University), Ministry of Education, Tianjin, PR China. Electronic address:

Miltiradiene serves as a pivotal precursor for the synthesis of numerous abietane-type diterpenes with important pharmacological activities. The endogenous mevalonate (MVA) pathway is tightly regulated in Saccharomyces cerevisiae, which limits the availability of precursors for the heterologous production of miltiradiene. In this study, the orthogonal isopentenol utilization pathway (IUP) was constructed and investigated for its adaptability with mitochondria and peroxisomes in S.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!