Award details

Generation of new natural and non-natural lantibiotics by genome mining and pathway engineering

Reference	BBS/E/J/0000A158
Principal Investigator / Supervisor	Professor Mervyn Bibb
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	70,644
Status	Completed
Type	Institute Project
Start date	02/02/2004
End date	01/02/2006
Duration	24 months

Abstract

The defining feature of lantibiotics is their possession of (methyl)lanthionine ring structures. All lantibiotics are derived from a ribosomally-synthesized prepeptide that is subject to post-translational modification by one or more modification enzymes. The gene clusters for lantibiotic synthesis also contain genes which have been implicated in export, cleavage of the leader peptide, immunity and regulation. Cinnamycin is a representative of the cinnamycin/duramycin/ancovenin subclass (class B) produced by the actinomycetes. This is an important series of compounds, duramycin being currently in phase II clinical trials for use in cystic fibrosis. Because of the nature of their biosynthesis, lantibiotics lend themselves to structural modification by changes to the small propeptide gene region. Our role in this collaborative project is to understand in closer detail how a representative set of pathway genes function (using the cinnamycin biosynthetic genes, which we have recently cloned and sequenced), but we will contribute from our knowledge base to the identification and analysis of novel lantibiotic pathways from actinomycete strains and the development of an optimised expression system for generation of lantibiotic variants. At the end of the project we will have established a new technical and knowledge platform on which to base further strategies for generating lantibiotic diversity, including information about both natural and artificial evolution of gene sets.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
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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