Penicillin Production - DCU

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• Reasonable heat-transfer. • Prevention of aggregation without damaging microorganisms. • Good bulk-flow and mixing to prevent the creation of dead zones in the reactor. • Good nutrient transfer. Economic: • Easy to operate aseptically. • Reasonably flexible regarding process requirements. • Low power consumption. • Stable under fluctuating conditions. • Cheap, robust, simple and well understood for scale-up. Below is an example of a typical reactor configuration: However, before we examine the above design, we need to take a step backwards to define some of the above terms. Mass Transfer is seen when there is mixing between two components of varying concentrations. A good example is a small amount of dye being dropped into a bucket of water. Mass Transfer processes are responsible for the movement of the dye through the water until equilibrium is reached. 1 This is very important when we are attempting to grow aerobic microbes in media. When the oxygen is bubbled through the fermenter tank, there will be high concentrations of oxygen near the bubbles but low concentration everywhere else in the tank. Since oxygen concentration is such a 1 Bioprocess Engineering Principles, Pauline M. Doran. 6
vital component of aerobic metabolism, it is essential that there is good transfer of oxygen across the gas/liquid interface. The Sparger delivers this oxygen. One problem with gas/liquid interfaces is the formation of foam. The impeller that serves to break up the foam generally relieves this. Heat Transfer is important because metabolism as a process tends to give off heat, as does the mechanical mixing by the impellers. If the reactor needs to be operated at a constant temperature of range of temperatures, then it is critical that there is some kind of system to cool the reactor. This is normally achieved through a combination of a cooling jacket and cool water being passed around the tank. Bulk Flow and Mixing are achieved by the impellers. Most reactors use the Rushton Flat-bladed disc turbine seen in the diagram. Fluid flow in a reactor can be described as Newtonian or non-Newtonian. Newtonian fluids show constant viscosity and linear shear rate against shear stress. However many fluids are non-Newtonian and are described as Bingham or Pseudoplastic. Batch, Fed-Batch and Continuous Culture are terms used to describe how nutrients and substrate will be delivered to a culture in a reactor. Batch simply means that a fixed amount of substrate is added at the beginning of the process. Fed Batch means that substrate is added in small increments at various times in the fermentation. Continuous means that substrate is constantly added to the reactor while an equal amount of fermented medium is removed. Steam is used to keep the reactor running aseptically. This is achieved because the reactor is designed as a pressure vessel and steam is sent through at a minimum temperature/pressure of 121 0 C/15 psi for 15-30min. So much for our discussion of basic reactor design. What follows is a brief description of the specific fermentation conditions necessary for the production of penicillin. Special fermenter Conditions for the production of <strong>Penicillin</strong> Aside from what is described above, there are a few specific characteristics of penicillin that must be considered when attempting fermentation: • Most penicillins form filamentous broths that are pseudoplastic (non- Newtonian) in nature. This means they can be difficult to mix due to their high (and not constant) viscosity. Also the increasing viscosity of the broth can hinder oxygen transfer. Which leads to the next point. • <strong>Penicillin</strong> is an aerobic organism; therefore the rate of oxygen supply is critical to the fermentation. Thus, the reactor must have an efficient oxygen supply system. 7
Page 1 and 2: Penicillin Production Tom O’Hare
Page 3 and 4: Penicillin G Penicillin G is not st
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Page 9 and 10: to survive. It is these conditions
Page 11 and 12: the cells should be showing filamen

Penicillin Production - DCU

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