Award details

Biosynthetic Origins and Utility of the Natural Product Antibiotic Nybomycin

Reference	BBS/E/J/000CA584
Principal Investigator / Supervisor	Professor Barrie Wilkinson
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	75,979
Status	Current
Type	Institute Project
Start date	09/01/2015
End date	08/01/2017
Duration	24 months

Abstract

The bacterial natural product nybomycin was first reported in 1955 but did not find clinical utility. Nybomycin was rediscovered during a screen for substances active against multidrug-resistant Staphylococcus aureus M50 which identified an actinomycete fermentation extract with a curious activity profile. Specifically, nybomycin is inactive against strains carrying intact type-II topoisomerase genes and active against those with mutated genes. Unexpectedly, rather than select for further additional mutations to generate dual resistance, quinolone resistant strains treated with nybomycin reverted to quinolone sensitivity by reversion of the relevant mutation, albeit at a low rate. Due to these phenomena nybomycin was termed a ‘reverse antibiotic’. Nybomycin’s biogenesis has remained elusive and this research project will utilise chemical and genetic studies (genome sequencing, mutational analysis) to elucidate the biosynthetic pathway and enable bioengineering studies to access increased titres and novel analogs in order to provide starting materials for the semi-synthesis of second generation nybomycins.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology, Pharmaceuticals
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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