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Title: A study of transcriptional regulators involved in the control of secondary metabolism in Serratia sp. ATCC 39006
Author: Gristwood, T.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Serratia sp. ATCC 39006 (Serratia 39006) is a Gram-negative member of the Enterobacteriaceae that synthesises several secondary metabolites, including the red tripyrrole antibiotic, prodigiosin (Pig; 2-methyl-3-pentyl-6-methoxyprodigiosin) and the β-lactam antibiotic, carbapenem (Car; 1-carbapen-2-em-3-carboxylic acid). Pig is of clinical interest as it has been shown to have anticancer and immunosuppressive properties. However, the natural physiological role of Pig I the producing organisms is unclear. This study investigates the mechanism by which three transcriptional regulators (PigZ, PigS and PhoB) modulate secondary metabolism in Serratia 39006. PigZ, a TetR-family transcriptional repressor, is shown to differentially modulate Pig and Car production via the transcriptional regulation of an unusual four-component RND-family efflux pump. The putative ArsR/SmtB family regulator, PigS, which is linked to the Pig biosynthetic cluster, is also shown to be a transcriptional repressor that modulates Pig production via repression of novel target genes. Finally, this study investigates the mechanism by which the transcriptional activator, PhoB, upregulates secondary metabolism in response to phosphate limitation, via multiple inter-linked pathways. In conclusion, this study has furthered our understanding of the regulation of secondary metabolism in Serratia 39006 and a model is presented in which this additional information has been integrated into the previously proposed regulatory network.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available