Investigations of the cyclase enzymes involved in lantibiotic biosynthesis

ORGN 740

Moushumi Paul, Department of Chemistry, University of Illinois, Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801 and Wilfred A. van der Donk, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews, Urbana, IL 61801.
Lantibiotics are peptide antibiotics that contain lanthionine thioether bridges, generated by Michael addition of cysteines to dehydroamino acids in the pre-lantibiotic peptide. In class AI lantibiotics, post-translational modifications involve a multi-enzyme complex including the proteins LanB and LanC, dehydratases and cyclases, respectively, while class AII use LanM to carry out both transformations. We have previously shown that the LanC enzymes involved in subtilin and nisin biosynthesis, SpaC and NisC, respectively, contain stoichiometric amounts of zinc, implying a catalytic role. EXAFS analysis of SpaC suggests that two cysteines coordinate to the metal. EXAFS and ICP analysis of SpaC mutants replacing the conserved cysteines with alanines demonstrated that these cysteines are involved in zinc binding. Similar studies have been undertaken using LctM, the LanM protein involved in lacticin 481 biosynthesis. Mutants are being analyzed to determine if eliminating zinc binding leads to a loss in cyclization activity.

 

Proteins, Peptides, and Amino Acids
8:00 AM-12:00 PM, Thursday, August 26, 2004 Pennsylvania Convention Center -- 201A, Oral

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004