Integron and omics based acceleratation of industrial strain development

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

This project aims to provide a new set of enabling technologies which will create a step change in the speed and efficiency with which engineered microbes can be constructed for industrial application. This improvement will be achieved by combining novel methods to recombine genes within the genome of industrial organisms with advanced metabolomics techniques and direct screening methods to identify strains with improved process efficiency. The project output will provide methods to overcome the normally time-consuming and laborious empirical process of iterative strain improvement. The initial application is to rapidly improve yeast strains used for bioethanol production but the suite of enabling tools being employed would be capable of accelerating the development of microbes for virtually any industrial application

Technical Summary

This project aims to provide a new set of enabling technologies which will create a step change in the speed and efficiency with which engineered microbes can be constructed for industrial application. This improvement will be achieved by combining novel methods to recombine genes within the genome of industrial organisms with advanced metabolomics techniques and direct screening methods to identify strains with improved process efficiency. The project output will provide methods to overcome the normally time-consuming and laborious empirical process of iterative strain improvement. The initial application is to rapidly improve yeast strains used for bioethanol production but the suite of enabling tools being employed would be capable of accelerating the development of microbes for virtually any industrial application

Planned Impact

The UK manufactures over 1 billion gallons of bioethanol and the US >12B gallons currently but mandated to increase to over 30 billion gallons by 2022. Despite controversy over the use of food crops for fuel, economic and political factors will dictate bioethanol policy for decades. It is now critical for science to improve ethanol production efficiency from current carbon sources, and adapt production microbes to new carbon sources. This project will greatly impact both issues by accelerating the genetic adaptation of commercial yeast strains to unused carbon in corn or other raw materials used to manufacture bioethanol and to greatly reduce or eliminate the need for added enzymes. This project will utilise a novel, efficient and versatile means to recombine fragments of DNA, along with metabolomics analyses to accelerate the genetic construction and improvement of yeast of extremely high commercial importance in biofuel manufacture. However, the method is potentially applicable to microbial strains for many industrial purposes. This project will provide new scientific advances and state of the art techniques in: 1) Tools for rapid strain improvement and pathway engineering 2) Engineered strains for bioethanol production 3) New assays and screens for bioethanol producing strains 4) Novel insights into the metabolome of industrialy important strains. Following appropriate protection of IP, the success of the project will be publicised widely by the academic groups in high impact scientific journals and through presentations at international symposia focussed on the applications of omics and genetic technologies.
This project has a direct route to market via the industrial partner Ingenza. Ingenza has established relationships with three current US bioethanol manufacturers who are prepared to evaluate and potentially implement the output of the project, thereby offering an attractive route to market without a significant change in the business model of the end users. One manufacturer has signed an agreement to test Ingenza's improved strains in its facilities to demonstrate feasibility. These manufacturers are part of a consortium with access to 25 bioethanol plants, representing approximately 5% of total US bioethanol production. The broader economic impact of the project will improve the economic sustainability, adaptability and robustness of the biofuel and subsequently other industries which use renewable feedstocks, reducing fossil fuel, land and fertiliser usage. Successful implementation of the project results and greater predictability in bioprocess improvement will encourage uptake of bioscience technology in the UK, by manufacturing sectors such as medicine, agriculture and personal care which apply these approaches to a degree but consider bioscience to be unpredictable in cost and timeline. This will positively impact the economic sustainability, adaptability and robustness of UK manufacturing with no negative social or environmental impact.
The project results will accelerate microbial strain improvement strategies aimed at the more efficient production of biofuels from diverse sources of biomass but will also provide methods to optimise the expression of any endogenous or heterologous proteins in microbial systems. Such improvements would have applications across many industrial sectors that include the production of proteins as biocatalysts or biologics, and the engineering of more complex biochemical pathways to produce secondary metabolites, nutritional supplements or natural products currently sourced from regions endangered by climate change, political or other factors. The technology may also have future application to the production of chemicals, which are out of scope for this competition and so will not be addressed directly in the proposed project.

Publications

10 25 50
publication icon
Olorunniji FJ (2017) Multipart DNA Assembly Using Site-Specific Recombinases from the Large Serine Integrase Family. in Methods in molecular biology (Clifton, N.J.)

publication icon
Olorunniji FJ (2016) Site-specific recombinases: molecular machines for the Genetic Revolution. in The Biochemical journal

Related Projects

Project Reference Relationship Related To Start End Award Value
BB/K011499/1 01/11/2012 31/10/2013 £248,848
BB/K011499/2 Transfer BB/K011499/1 01/11/2013 31/10/2015 £144,643
 
Description The technology developed during this project has been taken up and used by our collaborating company Ingenza. In collaboration we have improved industrial yeast strains for bioethanol production. The IP situation is under discussion.
Exploitation Route Ingenza our industrial partner is taking this technology forward in a range of industrially relevant strains and projects with large multinationals e.g. GSK
Sectors Chemicals,Energy,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The technology developed during this project has been taken up and is being used by our collaborating company Ingenza. They are using this technology in house to work with large multinational companies such as GSK. In collaboration, as a proof of concept, we have improved industrial yeast strains for bioethanol production. The outputs of this work have resulted in additional funding from the Scottish Government funded Industrial Biotechnology Innovation Centre to continue to refine the work to use the technology developed on an industrial yeast strain to improve a viable industrial process. The IP situation is still under discussion but the know how generated is being used in both the industrial and academic labs.
First Year Of Impact 2016
Sector Chemicals,Energy,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description Industrial Biotechnology Innovation Centre Accelerate Award
Amount £219,170 (GBP)
Organisation Industrial Biotechnology Innovation Centre 
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 11/2016
 
Title Novel methods for gene assembly 
Description We have developed (and are continuing to develop) new methods for rapid efficient assembly of DNA fragments using serine integrases. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact First version of the method is published (S.D. Colloms et al., Nucleic Acids Res. 42, e23).