Investigating the link between antibiotic production and compartmentalisation in Streptomyces coelicolor

Moye, Daniel Connor (2024) Investigating the link between antibiotic production and compartmentalisation in Streptomyces coelicolor. Doctoral thesis, University of East Anglia.

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Abstract

Production of secondary metabolites with antimicrobial properties is a means by which microorganisms can gain a competitive edge over their neighbours when in competition for resources. Members of the Streptomyces genus are excellent producers of bioactive secondary metabolites with more than 10,000 already characterized, influencing almost all areas of biology. Interestingly however, it is clear through genomic analysis we have barely scratched the surface of the potential of the Streptomyces genus for secondary metabolite production, with the vast majority of biosynthetic gene clusters silent under normal laboratory conditions.

In the model organism S. coelicolor, the products of only 4 of the predicted 29 biosynthetic gene clusters have been characterised. Whilst previous work has investigated the antibiotic properties of these metabolites, low antibiotic activity has been reported in solid media, and so the pigmented undecylprodigiosin and actinorhodin have been utilised more as genetic markers for mutagenesis experiments than for potential novel therapeutics. This raises a question of why colonies of S. coelicolor secrete these poor antibiotics at high levels when grown on solid media. Previous work in the Kelemen lab has identified a potential link between actinorhodin production and cell division however, indicative actinorhodin may also perform a regulatory function.

In this work the function of actinorhodin within S. coelicolor is investigated through the design, generation, and confirmation of actinorhodin biosynthetic gene cluster knockouts within S. coelicolor. Comparison between the wild-type and knockout colonies indicates actinorhodin production has a significant effect on colony phenotype, investigating both colony size and new colony development as a measure of fitness, as well as the localisation of actinorhodin production through employment of fluorescent fusion proteins. The results highlight a strong link between antibiotic production and compartmentalisation by cell division, perhaps highlighting actinorhodin may function in a previously uncharacterised mechanism of S. coelicolor colony self-regulation.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Nicola Veasy
Date Deposited:	12 Nov 2024 14:55
Last Modified:	12 Nov 2024 14:55
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97656
DOI:

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