BIOL 257 |
| Lantibiotics are highly effective peptide-derived antimicrobial agents with nanomolar MICs against pathogenic bacteria. These compounds are ribosomally synthesized and post-translationally modified to install multiple cyclic thioethers as well as dehydro amino acids. 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. We have recently succeeded in the reconstitution of the biosynthesis of nisin (1) as well as the new two-component lantibiotic haloduracin (2). Furthermore, the X-ray structure of the nisin cyclase was solved, which surprisingly revealed structural homology to farnesyl transferase. The implications of this finding will be discussed as will re-engineering efforts of the structure of lantibiotics. These studies demonstrate that the biosynthetic enzymes have very relaxed substrate specificity that has been exploited to generate analogs. 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.
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Antibiotics
9:00 AM-11:40 AM, Thursday, August 23, 2007 BCEC -- 109A, Oral
Division of Biological Chemistry |