Yaxley, Alice M. (2009) Study of the complete genome sequence of Streptomyces scabies (or scabiei) 87.22. PhD thesis, University of Warwick.

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Abstract

A study of the complete genome sequence of Streptomyces scabies 87.22, a common causative agent of scab disease of tubers including potato (Solanum tuberosum), is described. This work includes annotation of the genome and in-depth description of gene clusters likely to encode biosynthetic pathways for complex natural products and not also found in either “Streptomyces coelicolor” A3(2) or Streptomyces avermitilis MA-4680. Twenty-eight gene clusters were identified as likely to encode enzymes for the biosynthesis of complex natural products. Substances predicted by this work, not previously known to be made by S. scabies 87.22, were confirmed by collaborators as products - desferrioxamines, germicidins, and hopene. Of the clusters identified, fourteen gene clusters are not conserved in the other two streptomycete genome sequences for which comparisons have been undertaken. The Streptomyces genus is a reservoir of producer organisms from which many complex natural products of therapeutic importance have been isolated. These findings suggest that the cargo of cryptic and silent gene clusters amongst other members of this genus may add significantly to previous estimates of undiscovered bioactive natural products. Methods developed in this work could enable other researchers to rapidly identify gene clusters likely to encode enzymes involved in biosynthesis of complex natural products from complete genome sequences. De-replication is a problem for approaches to drug discovery based on activity screening and isolation of wild producer organisms. Computational methods in this work allow rapid de-replication of gene clusters following sequencing which may lead to discovery of many new natural products with therapeutic benefit. Sequences predicted to be involved in scab disease pathogenicity are not found in only one ‘pathogenicity island’ location as expected, but at several loci. Two possible mechanisms were identified from sequence data which it is suggested could be involved in regulation of pathogenicity traits: an MbtH-like protein family and an iron box sequence likely to be triggered response to low iron conditions.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	Streptomyces scabies -- Genome mapping, Biosynthesis
Date:	June 2009
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Wellington, E. M. H. (Elizabeth M. H.), 1954- ; Allaby, Robin
Extent:	xviii, 1, 223 leaves : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/3832

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