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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Wilfred van der Donk, University of Illinois at Urbana-Champaign
Post-translational modifications in natural product biosynthesis
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 succeeded in the reconstitution of the biosynthesis of nisin1 as well as the new two-component lantibiotic haloduracin.2 The X-ray structure of the nisin cyclase was solved, which surprisingly revealed structural homology to farnesyl transferase. The implications of these findings will be discussed as will re-engineering efforts of the structure of lantibiotics and investigations into their mode of action.3,4 These studies demonstrate that the biosynthetic enzymes have very relaxed substrate specificity that has been exploited to prepare a range of compounds from lantibiotics to conotoxin and enkephalin analogs.
(1) 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) 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.
(3) Levengood, M. R.; Knerr, P. J.; Oman, T. J.; van der Donk, W. A. J. Am. Chem. Soc. 2009, 131, 12024-12025.
(4) Oman, T. J.; van der Donk, W. A. ACS Chem. Biol. 2009, 4, 865-874.
For more information contact Prof. Wendy Kelly (404-385-1154).
