LAntibiotic Production: Technology, Optimization and improved Process
Lead Research Organisation:
John Innes Centre
Department Name: UNLISTED
Abstract
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Technical Summary
The aim of this project is to analyse the regulation of lantibiotic biosynthesis in actinomycetes. Lantibiotics are ribosomally synthesised peptide antibiotics that undergo a variety of post-translational modifications. The project will focus on NAI-107 (also known as microbisporicin) produced by Microbispora sp. The aim is to understand how the production of this compound is activated, and to dissect the roles, and relationships between, both pathway-specific and global regulatory genes. The interaction between lantibiotic biosynthesis and self-resistance will also be analysed.
Planned Impact
unavailable
Organisations
People |
ORCID iD |
| Mervyn Bibb (Principal Investigator) |
Publications
Fernández-MartÃnez LT
(2015)
A relA-dependent regulatory cascade for auto-induction of microbisporicin production in Microbispora corallina.
in Molecular microbiology
Fernández-MartÃnez LT
(2014)
Use of the meganuclease I-SceI of Saccharomyces cerevisiae to select for gene deletions in actinomycetes.
in Scientific reports
| Description | We have discovered how an unusual antibiotic (microbisporicin) with clinical potential is made, and how that process is controlled. We identified two positively acting regulatory genes, and one negative regulatory gene. We also identified an immunity mechanism that the producing organism uses to protect itself from the antibiotic, and have shown that if we knock that out, the strain does not die, but fails to produce the compound. That is, it has evolved a safety mechanism to protect itself from potentially committing suicide. |
| Exploitation Route | Over-expression of the two positively acting regulatory genes resulted in significant increases in productivity. This has resulted in an improved industrial process for microbisporicin which will be crucial as this compound proceeds to Phase I clinical trials. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | The knowledge and strains that we produced have been incorporated into an industrial scale fermentation process to produce enough microbisporicin for pre-clinical development. |
| First Year Of Impact | 2013 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic |