Monday, July 30, 2007 - 2:00 PM
S50
Biosynthesis of the lantibiotics nisin and haloduracin
Wilfred A. Van der Donk, Chemistry, University of Illinois, 600 South Mathews Ave, Urbana, IL 61801
Lantibiotics are highly effective peptide-derived antimicrobial agents with nanomolar MICs against pathogenic bacteria. These compounds are ribosomally synthesized and post-translationally modified by a multienzyme complex. Nisin has been used for decades in the food industry against food-borne pathogens. The compound has attracted much attention due to its novel mechanism of action including specific binding to the bacterial cell wall precursor lipid II, followed by membrane permeabilization. We have recently succeeded in the reconstitution of the biosynthesis of nisin1 as well as the new two-component lantibiotic haloduracin.2 Furthermore, we have determined the X-ray structure of the nisin cyclase, which surprisingly reveals structural homology to farnesyl transferase. The implications of this finding will be discussed as will re-engineering efforts of lantibiotics and the mechanism of their biosynthesis.
1. Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis. Li, B.; Yu, J.-P. J.; Brunzelle, J. S.; Moll, G. N.; van der Donk, W. A.; Nair, S. K. Science 2006 311, 1464-1467.
2. Discovery and in vitro biosynthesis of haloduracin, a new two-component lantibiotic. McClerren, A. L.; Cooper, L. E.; Quan, C.; Thomas, P. M.; Kelleher, N. L.; van der Donk, W. A. Proc. Natl. Acad. Sci. USA 2006 103, 17243-17248.
1. Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis. Li, B.; Yu, J.-P. J.; Brunzelle, J. S.; Moll, G. N.; van der Donk, W. A.; Nair, S. K. Science 2006 311, 1464-1467.
2. Discovery and in vitro biosynthesis of haloduracin, a new two-component lantibiotic. McClerren, A. L.; Cooper, L. E.; Quan, C.; Thomas, P. M.; Kelleher, N. L.; van der Donk, W. A. Proc. Natl. Acad. Sci. USA 2006 103, 17243-17248.