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Department of Genetics and Microbiology, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK
Department of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
Department of Biology, University of York, York YO1 5DD, UK
Department of Biochemistry and Biological NMR Centre, University of Leicester, Leicester, UK
5Author for correspondence: H. M. Dodd. Tel: +44 1603 255243. Fax: +44 1603 507723. e-mail: DODDH@BBSRC.AC.UK
ABSTRACT
The genetic determinants controlling immunity to nisin are coordinately regulated, along with biosynthesis genes, in response to an environmental signal, nisin or a nisin analogue. The nisR gene product, the putative response regulator of nisin biosynthesis, was found to be a vital component of this induction mechanism. This protein forms part of a two-component regulatory system which controls the expression of genes involved in nisin immunity and biosynthesis. Analysis of the structural requirements of the external signal, using nisin fragments and engineered nisin variants, indicated that the 12 amino-terminal residues of the molecule are a minimum requirement for induction, with an intact ring A being an essential component. Changes throughout the molecule also affected its induction capacity. The production of certain variant nisins by engineered lactococcal strains is reduced in paralle with the strains’ immunity to nisin. This can be attributed to inefficient induction by the variant molecule. Treating growing cultures with nisin restored full immunity and maximized the yields of nisin variants by the producer strains.
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