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Title: Engineering characterisation and implementation of pH control in microscale Saccharopolyspora erythraea fermentations
Author: Elmahdi, I.
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
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Microscale operations are rapidly emerging as a useful tool for reducing the time and cost involved in fermentation process development. For both microbial and mammalian fermentations pH is a vital process parameter since it has a marked affect on cell growth rate, viability and product synthesis. It is the objective of this thesis to investigate the influence of pH on growth and erythromycin synthesis by Saccharopolyspora erythraea CA340 and implement an automated pH control system at the microscale. The engineering properties of mixing and gas-liquid mass transfer in a 24-well microtitre plate system were characterised. k ,a values up to 0.014 s"1 could be obtained for a soluble complex medium (SCM) and generally increased with increasing shaking frequencies and decreasing fill volumes. Similar trends were identified for measured liquid phase mixing times which were around 5-2284 s under operational conditions. The influence of different fermentation media types oil based medium (OBM), starch based medium (SBM), and SCM and various pH control strategies on growth and erythromycin synthesis by S. erythraea at the 7 L and 5 L scales were next investigated. Faster rates of growth were achieved during fermentations carried out with the SCM and SBM, with the maximum specific growth rate (umax) reaching 0.12 h"1. Growth rates were slower in the more viscous OBM, but erythromycin A titres were double those obtained with the SCM and SBM, however, the long mixing times and high viscosities associated with growth on OBM made this medium unsuitable for microwell fermentations of S. erythraea CA340. At the 7 L scale the implementation of base only or full pH control (NaOH and H3PO4 additions) increased both the maximum growth rate and erythromycin concentrations attained compared to fermentations without pH control. The effects were accurately reproduced in manually pH-controlled microwell fermentations (1000-fold scale translation). The outcome of these studies led to the specification of an automated pH control system at the microscale using a LabView-based software controller integrated with a robotic liquid handling system to monitor and control the pH during microwell fermentations. A specially designed microwell plate was built that allowed the insertion of a micro-pH probe into each well (total well volume 7 mL) and was used during automated pH controlled microwell fermentations. The implementation of base pH control at the microwell scale led to almost one and a half fold increase in both biomass yield and erythromycin A production. It also enabled the operation of a fed-batch process at the microwell scale which further increased erythromycin A production by 60 %. The prototype system thus has the potential to support fermentation process development at the microwell scale.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available