Cull, Stephen Geoffrey;
(2003)
Process selection and design for the microbial biotransformation of poorly water-soluble nitrile compounds.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The biotransformation of poorly water-soluble aromatic dinitriles is of scientific and industrial interest. Although processes do exist for the transformation of water-soluble compounds, such as acrylonitrile, no description of a process suitable for the large scale biotransformation of poorly water soluble nitriles currently appears in the literature. This work investigates the systematic design and optimisation of a process for the production of 3-cyanobenzamide from the poorly water soluble 1,3-dicyanobenzene (1,3-DCB) and defines criteria for successful scale-up of the process to 75 L scale. A two-liquid phase process was initially designed at the laboratory scale (10 mL) which utilised the nitrile hydratase (NHase) activity of a whole cell Rhodococcus R312 biocatalyst. Toluene was selected as the carrier solvent and the process was optimised for amide production. This allowed the definition of a suitable operating window where the maximum space-time yield of amide formation could be obtained. The use of a room temperature ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate [bmim]PF6, was also investigated for the first time as a potential replacement for organic solvents in such multiphase bioconversion processes. Transformations carried out in aqueous-ionic liquid systems showed similar kinetic profiles for amide and acid production and enhanced stability of the whole cell biocatalysts. Scale-down studies on the hydrodynamics of the bioconversion process at 3 L and 75 L scales in geometrically similar vessels were performed. On-line measurements of droplet size distribution were used to investigate the dynamic variation of droplet size distributions as a function of dispersed phase volume fraction and agitation rate. This allowed the definition of constant power input per unit volume as a scale-up basis for the maintenance of mean droplet size at each scale. Based on this understanding of the reactor hydrodynamics the reliable scale-up of 1,3-DCB bioconversion from the 3 L to 75 L scales was finally demonstrated.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Process selection and design for the microbial biotransformation of poorly water-soluble nitrile compounds |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Applied sciences; Aromatic dinitriles |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10098940 |
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