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Exploration of novel molecular communication systems in Streptomyces
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Harwood, Matthew Paul (2023) Exploration of novel molecular communication systems in Streptomyces. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3985050
Abstract
Microbial hormones are small molecules involved in the regulation of clinically and industrially relevant antimicrobials, anticancer and antiparasitic compounds. The Actinomycetota phylum contain numerous ArpA-like TetR Family of Transcriptional Regulators (TFTRs) that are critical in controlling the biosynthesis of these important clinical and industrial compounds. This is achieved through complementary interaction with their respective hormones in a concentration-dependent manner, influenced by the exogenous population, making these systems fundamental in quorum sensing. In this investigation, we logically classified ArpA-like receptors across the Actinomycetota phylum based on their predicted hormone binding partner molecules and used this to guide the discovery, purification and characterisation of Streptomyces iakyrus butyrolactone (SIB), a novel class of microbial hormone from Streptomyces iakyrus containing an oxidised alkyl chain. Furthering this work, we were able to logically extend existing understandings of microbial hormone biosynthesis based on gene architecture and use this to isolate novel microbial hormones from Streptomyces rishiriensis and Streptomyces ambofaciens, controlling lactonamycin and kinamycin, respectively. To support the heterologous isolation of these novel hormones, we engineered two novel Streptomyces superhosts based on S. coelicolor M1152 that no longer produces any microbial hormones, creating cleaner heterologous hosts. This investigation has provided a computational and biological platform for the future isolation and exploration of microbial hormones and has demonstrated the potential for a vast level of structural diversity within these systems. Our new hosts will support the natural product community and our discovery of a new hormone system will hopefully lead to the manipulation of more SIB systems and the isolation of novel bioactive compounds.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology |
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Library of Congress Subject Headings (LCSH): | Hormones -- Synthesis, Streptomyces, Genetic transcription -- Regulation, Genetic regulation, Cellular signal transduction, Bacterial genetics | ||||
Official Date: | July 2023 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Corre, Christophe ; Wellington, E. M. H. (Elizabeth M. H.), 1954- | ||||
Format of File: | |||||
Extent: | 376 pages : colour illustrations | ||||
Language: | eng |
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