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Towards the minimum host cell for biocatalysis: global integrative analysis of gene expression to identify genes conferring cell stability

Reference	BB/C503346/1
Principal Investigator / Supervisor	Professor Royston Goodacre
Co-Investigators / Co-Supervisors	Professor Gillian Stephens, Professor Gordon Tiddy
Institution	The University of Manchester
Department	Chemistry
Funding type	Research
Value (£)	412,143
Status	Completed
Type	Research Grant
Start date	01/10/2004
End date	31/12/2007
Duration	39 months

Abstract

Supervised learning algorithms will be used to identify the genes that control the stability of whole cell biocatalysts. The information will be used to design a metabolically engineered host cell with improved substrate and product resistance, thus providing a step change in the productivity of industrial redox biotransformations. We shall analyse biocatalyst performance in experimental biotransformations using toluene dioxygenase, and other enzymes, expressed as E. coli. The genes conferring good or bad performance will be identified by analysis of the transciptome, proteome and metabolome under a range of process conditions, focussing especially on the effect of varying substrate physical properties. The data will be analysed using evolutionary computing so that biocatalyst performance can be linked to the omic data. The genes conferring resistance and sensitivity to substrates and products will be identified and their importance ranked, together with other determinants of biocatalyst performance (e.g. cofactor recycling, in vivo enzyme stability etc). The most important genes will be targetted to construct metabollically-engineered hosts for experimental verification of the predictions.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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