Award details

14TSB_SynBio A toolchest for rapid bootstrapping of novel chassis organisms

Reference	BB/M005607/1
Principal Investigator / Supervisor	Professor John Ward
Co-Investigators / Co-Supervisors
Institution	University College London
Department	Biochemical Engineering
Funding type	Research
Value (£)	99,927
Status	Completed
Type	Research Grant
Start date	18/08/2014
End date	17/07/2015
Duration	11 months

Abstract

We will develop rapid tools, techniques and materials to enable the construction of novel expression systems in a new chassis. The chassis organisms will be chosen from several Gram positive and Gram negative bacteria whose characteristics make them more suited to industrial bioprocess conditions than E. coli. Promoters from highly expressed genes will be searched for using bioinformatics tools developed by Synthase. These promoters will be synthesised, tested in the new chassis with a reporter gene and modularised for later use in building expression constructs. Ribosome binding sites will be similarly designed synthesised, tested and modularised. Genes to be expressed will be chosen with regard to the chassis. For example enzymes for biocatalysis and for building pathways for chiral chemical synthesis will be designed for a chassis that can tolerate organic solvents or high concentrations of the substrate. Genes will be codon optimised for the new host and the new expression systems will be subjected to multifactorial experimental design to iterate between testing, design and implementation to deliver robust expression systems that can be rapidly built for a new chassis.

Summary

New organisms for the expression of recombinant genes are needed. Organisms that have a greater resistance to the conditions in biocatalysis for the synthesis of pharmaceutical compounds are needed. We want to move from a petrochemical based chemical and pharmaceutical synthesis to a more bio-based economy and to do this we need much better and more rapid tools for building biochemical and metabolic pathways in a new organism (chassis). The proposed project will develop rapid ways of getting high level expression in any new chassis organism. The various steps of enzyme expression will be dissected using our new tools and knowledge of how genes are expressed. This will lead to modular parts for the expression of biocatalysis genes and pathways in any new chassis. We will test this development pathway in some selected chassis that are examples of novel organisms more fitted to the bioprocess conditions for the bio-synthesis of pharmaceutical compounds.

Impact Summary

The impact of this work will be in the growing bio-economy whjere we want to decrease our reliance on petrochemical based feedstocks for the production of all chemicals, pharmaceuticals and polymers. If we want to increase the use of biologically derived materials both as inputs and for the generation of materials by biocatalysis and through new synthetic metabolic pathways, then these new tools will aid these goals. The UK fine chemical and pharmaceutical industry would benefit by having an increased number of tools and methods for it to use for the bio-synthesis of compunds. The UK economy would benefit by keeping the manufacture and research in these areas, within the UK and also to keep in a leading position in the new technologies in synthetic biology.

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology, Synthetic Biology, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	Innovate UK (TSB) [2011-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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