Award details

13TSB SynBio Use of Synthetic Biology methods to enhance and optimise production of a novel antibiotic

Reference	BB/L004348/1
Principal Investigator / Supervisor	Professor Mervyn Bibb
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	Molecular Microbiology
Funding type	Research
Value (£)	171,795
Status	Completed
Type	Research Grant
Start date	01/10/2013
End date	31/03/2015
Duration	18 months

Abstract

Demuris has a pipeline of novel antibiotics produced by a variety of different actinobacteria. The leading molecule is presently made by an organism that is not ideal for large scale fermentation, and the compound structure may not yet be optimal in terms of pharmacological properties. We wish to identify the antibiotic biosynthetic gene cluster and re-engineer it for production in a heterologous expression host specifically engineered for production of actinobacterial natural products that is based on Streptomyces venezuelae. Pathway engineering in S. venezuelae will then be used to generate analogues of the lead antibiotic, which will be used to facilitate drug optimization and IP protection

Summary

Demuris has a pipeline of novel antibiotics produced by a variety of different actinobacteria. The leading molecule is presently made by an organism that is not ideal for large scale fermentation, and the compound structure may not yet be optimal in terms of pharmacological properties. We wish to identify the antibiotic producer gene cluster and re-engineer it for production in an optimized chassis for production of actinobacterial natural products based on Streptomyces venezuelae (Sven). Pathway engineering will be used to generate analogues of the lead antibiotic, which will be used to facilitate drug optimization and IP protection

Impact Summary

The project would impact directly on the core business of Demuris by supporting and accelerating the development of its leading compounds through key value inflection points at a rate not currently achievable within the company's budget and resources. Demuris currently does not have dedicated scientists working on genetic manipulation of its antibiotic producer strains, let alone applying synthetic biology methods. The funding will allow Demuris to build capacity and expertise in an area that could profoundly enhance its competitive position. Although Demuris is making rapid progress, full exploitation of the opportunities for commercialisation of the Demuris actinomycete collections will require a significant VC funding round. Additional R&D Grant support would be a key signal for investors that the project is viable and that Demuris and its employees have the relevant skills and experience to succeed. Further investment in drug discovery at Demuris would generate high quality jobs and facilitate wealth creation in the North East of England, an area of high unemployment and economic deprivation. There are clear social and economic benefits of developing new antibiotics, by reducing length of time in hospital and mortality. Increased productivity and life expectancy will add value to the UK economy. Funding from TSB for this project will also enable JIC to fulfil its institutional commitment to Knowledge Exchange and Commercialisation, mandated by BBSRC, allowing it to transfer its knowledge and technical expertise in the genetic manipulation of streptomycetes into an industrial setting, and assist, in a tangible way, the development of a UK-based SME, Demuris.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Industrial Biotechnology, Microbiology, Pharmaceuticals, Synthetic Biology
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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