The robustness of bioprocesses is becoming increasingly important. The main driving forces of this development are, in particular, increasing demands on product purities as well as economic aspects. In general, bioprocesses exhibit extremely high complexity and variability. Biological systems often have a much higher intrinsic variability compared with chemical processes, which makes the development and characterization of robust processes tedious task. To predict and control robustness, a clear understanding of interactions between input and output variables is necessary. Robust bioprocesses can be realized, for example, by using advanced control strategies for the different unit operations. In this review, we discuss the different biological, technical, and mathematical tools for the analysis and control of bioprocess robustness.
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http://dx.doi.org/10.1016/j.tibtech.2023.03.002 | DOI Listing |
mSystems
January 2025
Biosystems and Bioprocess Engineering, IIM-CSIC, Vigo, Spain.
During batch fermentation, a variety of compounds are synthesized, as microorganisms undergo distinct growth phases: lag, exponential, growth-no-growth transition, stationary, and decay. A detailed understanding of the metabolic pathways involved in these phases is crucial for optimizing the production of target compounds. Dynamic flux balance analysis (dFBA) offers insight into the dynamics of metabolic pathways.
View Article and Find Full Text PDFBiotechnol Bioeng
January 2025
Bioprocess Research and Development (BRD), WuXi Biologics, Shanghai, China.
Serving as a dedicated process analytical technology (PAT) tool for biomass monitoring and control, the capacitance probe, or dielectric spectroscopy, is showing great potential in robust pharmaceutical manufacturing, especially with the growing interest in integrated continuous bioprocessing. Despite its potential, challenges still exist in terms of its accuracy and applicability, particularly when it is used to monitor cells during stationary and decline phases. In this study, data pre-processing methods were first evaluated through cross-validation, where the first-order derivative emerged as the most effective method to diminish variability in prediction accuracy across different training datasets.
View Article and Find Full Text PDFBioresour Technol
January 2025
Department of Chemical, Biological and Environmental Engineering, Engineering School, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain. Electronic address:
The present work introduces and validates an artificial cell free system for the synthesis of acetoin from ethanol, representing a greener alternative to conventional chemical synthesis. The one pot multi-enzymatic system, which employs pyruvate decarboxylase from Zymobacter palmae (ZpPDC), alcohol dehydrogenase from Saccharomyces cerevisiae (ScADH), and NADH oxidase from Streptococcus pyogenes (SpNOX), achieves nearly 100 % substrate conversion and reaction yield within 6 h under optimal conditions (pH 7.5, enzyme activities: ZpPDC 100 U·mL, ScADH 50 U·mL, SpNOX 127 U·mL, and 1 mM NAD).
View Article and Find Full Text PDFSci Total Environ
January 2025
Biotechnology Program, Center for Sustainable Development, College of Arts and Sciences, Qatar University, Doha 2713, Qatar. Electronic address:
Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polymers that can replace conventional plastics in different sectors. However, PHA commercialization is hampered due to their high production cost resulting from the use of high purity substrates, their low conversion into PHAs by using conventional microbial chassis and the high downstream processing cost. Taking these challenges into account, researchers are focusing on the use of waste by-products as alternative low-cost feedstocks for fast-growing and contamination-resistant halophilic microorganisms (Bacteria, Archaea…).
View Article and Find Full Text PDFJ Chromatogr A
January 2025
Lab Essentials Applications Development, Sartorius Lab Instruments GmbH & Co. KG, Göttingen, Germany.
Adeno-associated viruses (AAV) are among the leading vectors for in vivo gene therapy. The purification of AAV remains a bottleneck as it typically requires multiple individual process steps, often resulting in product loss and high costs. Current downstream processes are usually serotype-specific and rely primarily on expensive affinity resins.
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