Thesis

Improved routes to bioprocessing of biopharmaceuticals by a marine fungus

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Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13193
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Abstract
  • The marine-derived fungus, Trichoderma pseudokonningii was isolated from seawater at Oban, Scotland and provided by Aquapharm Biodiscovery Ltd. The aim of this project was to investigate a microorganism that can produce bioactive secondary metabolites as well as to develop efficient cultivation and production processes on a small scale which could be finally scaled up to a fermenter system. Current findings show that salinity has a very clear influence upon growth and sporulation of this fungus. A dereplication study of its secondary metabolites was carried out using - LTQ-Orbitrap-HRFTMS and high resolution NMR. With the aid of an automated label-free differential expression software, SIEVE v.1.2 and MZmine v.2.2, the presence of four bioactive compounds were identified including virescenoside B, gemfibrozil, γ-linolenic acid, and a lovastatin derivative. Scale-up of the production of the probably new lovastatin congener was chosen because of the high market value of lovastatin in the world. From LC-MS quantification results, PDA without the Instant Ocean (IO) gave the maximum yield of the lovastatin congener (6.13 μg/plate). NMR analysis also confirmed the presence of a structure related to lovastatin produced in cultures of AQP 4097 which has a difference in chemical shifts of the olefinic protons. Moreover, increasing the initial glucose concentration and dissolved oxygen tension in the medium promoted the growth of this strain; however, the higher agitation speed was associated with adverse affects both on mycelial morphology and production of the lovastatin derivative by AQP 4097. Slowly utilized carbon sources, such as glycerol, promoted the production of the lovastatin derivative, and also affected culture morphology of AQP 4097 which was transformed from loose fluffy aggregates into denser larger pellets within 72 hours after inoculation. Conclusively, a lovastatin derivative was successfully produced from the marine-derived fungus (Trichoderma pseudokonningii) by shake flask and fermentation vessel process. In the scale up of the production of the described lovastatin congener the appropriate conditions that include glucose consumption, dissolved oxygen, carbon source, and agitation speed have to be carefully considered in order to obtain the highest yield as well as to maintain the mycelial morphology.
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  • Strathclyde theses - ask staff. Thesis no. : T13193
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Date Created
  • 2012
Former identifier
  • 947650

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