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Developing the Mupirocin QS system of P fluorescens into an efficient and economical way to control industrial production of high value products

Reference	BB/M028739/1
Principal Investigator / Supervisor	Professor Christopher Thomas
Co-Investigators / Co-Supervisors
Institution	University of Birmingham
Department	Sch of Biosciences
Funding type	Research
Value (£)	841,021
Status	Completed
Type	Research Grant
Start date	01/07/2015
End date	30/06/2018
Duration	36 months

Abstract

The mupIRX gene system in Pseudomonas fluorescens regulates genes encoding the Mupirocin biosynthetic pathway, allows auto induction of gene expression and has already been manipulated to yield benefits for antibiotic production. We will define biochemical properties of the protein products and their DNA binding sites to allow more precise re-engineering of gene expression under the control of the positive regulator MupR and fine tuning of the N-acyl homoserine lactone quorum signal by expression of its synthase MupI and its modulation by MupX. We will test different configurations including a cascade controlled by mupR to induce expression of single genes encoding high value proteins and gene clusters encoding other biosynthetic pathways. We will optimise regulation via the quorum sensing (QS) circuitry and amplification of copy number of plasmids encoding key genes. The innovation is in exploiting the native QS system in an established and proven industrial host strain.

Summary

Industrial production of high value products by bacteria is a vital part of the modern biotechnology and pharmaceutical industries. Competition to produce such products as cheaply as possible means that the costs of the specialist chemicals added to fermenters to switch on production need to be controlled. The mupIRX gene system in Pseudomonas fluorescens regulates genes encoding the Mupirocin biosynthetic pathway, allows switch on of gene expression by an internal signal that accumulates as the bacteria grow and has already been manipulated to yield benefits for antibiotic production. We will define the elements of this control system to allow us to construct systems to put the production of other high value products under the control of this system. The innovation is in exploiting the native control system in an established and proven industrial host strain.

Impact Summary

As described in proposal submitted to IUK

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Industrial Biotechnology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Industrial Biotechnology Catalyst (IBCAT) [2014-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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