Award details

Antibiotic production in actinomycetes

Reference	BBS/E/J/00000607
Principal Investigator / Supervisor	Professor Mervyn Bibb
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	2,739,415
Status	Completed
Type	Institute Project
Start date	05/12/2003
End date	31/07/2016
Duration	151 months

Abstract

The major focus of my research group is an unusual and clinically unexploited class of peptide antibiotics (lantibiotics) made by streptomycetes and other high G+C actinomycetes. Work is in progress to understand the biosynthesis of cinnamycin (Streptomyces cinnamoneus), cypemycin (Streptomyces OH-4156), actagardine (Actinoplanes garbadinensis), microbisporicin (Microbispora corallina) and planosporicin (Planomonospora alba). Our ultimate aim is to develop fundamental insights that will allow us to use recombinant approaches to generate novel peptides with valuable pharmaceutical and agricultural applications. A second major area of interest is the regulation of secondary metabolism, particularly antibiotic production, in Streptomyces coelicolor and Streptomyces venezuelae, and its growth phase-dependence. A variety of molecular and genetic techniques, including global transcriptome and proteome analyses, are being applied to analyse the expression of gene clusters encoding several of the secondary metabolites made by these strains. In particular, the influence of growth rate, intracellular ppGpp and extracellular signalling molecules on the expression of pleiotropic and pathway-specific regulatory genes is being studied to elucidate regulatory networks and the underlying mechanisms of signal transduction. The recent sequencing of the complete genomes of several streptomycete species revealed the presence of a large number of "cryptic" secondary metabolic gene clusters, and led to the realisation that these organisms have the ability to produce many more natural products than had previously been recognised. One of the aims of our work is to identify the physiological signals and regulatory mechanisms responsible for the activation of these "cryptic" pathways, thus unleashing the full biosynthetic potential of these prodigious producers of valuable natural products. These studies are now being extended to include other "rare" actinomycete species.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology
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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