Genomics-led Discovery of Antimicrobials From Scytonema

Byrne, Nathan (2024) Genomics-led Discovery of Antimicrobials From Scytonema. Doctoral thesis, University of East Anglia.

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Abstract

Natural products are an important source of antibiotics and other clinically relevant compounds. Unfortunately, the rise of antibiotic resistance has rendered existing antibiotics ineffective in treating multidrug resistant pathogens. This development has coincided with a drop-off in the discovery of novel natural products. The combination of these two factors has created a desperate need for the discovery of novel bioactive molecules.

One barrier to finding novel bioactive molecules is the constant rediscovery of the same compounds which requires lengthy dereplication. By investigating understudied bacterial species, the chance of rediscovering an existing molecule is lower and thus the chance of finding something novel is higher. Scytonema are a genus of cyanobacteria of the order Nostocales. When the genome sequence for Scytonema hofmannii PCC 7110 was published it was the largest bacterial genome sequenced to date. The genome, over 12 MB, is predicted to produce over 30 specialised metabolites; only six molecules have been isolated from this strain. Apart from Scytonema hofmannii PCC 7110 very little is known about the rest of the Scytonema genus. Many Scytonema strains have no published literature about them, let alone investigations into their ability to produce specialised metabolites.

In this thesis, the ability of the Scytonema genus to produce novel specialised metabolites was investigated. The genomes of 10 strains of Scytonema were sequenced, where none had previously publicly available genomic information. These genomes were then analysed to elucidate their ability to produce novel specialised metabolites. Screening was undertaken to determine if these strains produced bioactive metabolites, and attempts were made to trigger the production of novel specialised metabolites. This work revealed two antimicrobial compounds. The first, a known compound, led to attempts to determine the biosynthetic gene cluster responsible for its production. The second, a novel compound, led to attempts to structurally characterise this molecule.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	03 Jun 2025 12:42
Last Modified:	03 Jun 2025 12:42
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99389
DOI:

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