Computational Modeling of Bacteriophage Production for Process Optimization. 2018

Konrad Krysiak-Baltyn, and Gregory J O Martin, and Sally L Gras
The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.

Computational models can be used to optimize the production of bacteriophages. Here a model is described for production in a two-stage self-cycling process. Theoretical and practical considerations for modeling bacteriophage production are first introduced. The key experimental protocols required to estimate key kinetic parameters for the model, including determining variable infection rates as a function of substrate concentration, are described. ppSim is an open-source R-script that can simulate bacteriophage production to optimize productivity or minimize costs. The steps included to run the simulation using the experimentally determined infection parameters are described. An example is also presented, where a level sensor and cycle time are optimized to maximize bacteriophage productivity in two sequential 1-L bioreactors, resulting in a production rate of 4.46 × 1010 bacteriophage particles/hour. The protocols and programs described here will allow users to potentially optimize production of their own bacteriophage-bacteria pairing by effectively applying bacteriophage modeling.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D001419 Bacteria One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive. Eubacteria
D001435 Bacteriophages Viruses whose hosts are bacterial cells. Phages,Bacteriophage,Phage
D019149 Bioreactors Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. Fermentors,Bioreactor,Fermentor

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