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Title: Bioprocess intensification of antibiotic production using functionalized polyhipe polymers
Author: Ndlovu, Teresa Manguangua
ISNI:       0000 0004 2720 4871
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2009
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This study used "Streptomyces coelicolor" A3(2) as a model organism to study the potential for process intensification in antibiotic production using solid phase growth. This organism produces three chromosomally encoded antibiotics, actinorhodin, prodigiosin, and calcium dependent antibiotic (CDA), and one plasmid encoded antibiotic methylamycin. In this study the production of prodigiosin was the focus for this process intensification. A novel technique was developed in the preparation of the bacterial support (PHP) , which ensures a well-controlled internal architecture. Solid phase growth on this matrix was shown to support the production of prodigiosin and actinorhodin. The growth of "Streptomyces coelicolor" A3(2) on this nano-structured, macro-porous, polymeric support with hierarchic connectivity, generically known as PolyHIPE polymer. Variations of PHP were investigated and compared with conventional flask growth; the production of prodigiosin in PHP was demonstrated to exceed that in flask growth, offering the potential for an order of magnitude improvement in volumetric productivity. A micro-bioreactor was designed to improve spore penetration, the distribution of cells, viability and nutrient supply. Growth was observed by electron microscopy, SEM and TEM. It was operated as a forced inoculation of pre-germinated spore suspension in modified R5 media, this micro-bioreactor enhanced productivity by an order of magnitude. This study shows that bacterial growth rate and secondary metabolism are influenced by the pore size and surface chemistry of the support material. To understand these surfaces and scale dependent phenomena a series of microporous structures with different functionalised surfaces were generated. An initial proteomic study was performed to determine whether solid phase culture had lead to a fundamentally different pattern of growth. One dimensional SDS gel electrophoresis revealed some variations in the pattern of protein bands between samples from growth in flasks and on the different PHP supports. Mass spectrometric analysis by peptide mass fingerprinting, of differentially observed bands, revealed the predominance of elongation factor EF-tu in liquid culture and increases in S-adenosylmethionine synthetase and hypothetical protein SC07276 in solid phase culture.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available