Investigation of substrate specificity of the bifunctional lantibiotic enzyme LctM

ORGN 661

Gregory C. Patton, gpatton@uiuc.edu, Champak Chatterjee, chatterj@uiuc.edu, and Wilfred A. van der Donk, vddonk@uiuc.edu. Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave, 147 RAL, Box 97-5, MC 712, Urbana, IL 61801
Lantibiotics are a unique class of ribosomally synthesized peptide antibiotics produced by Gram-positive bacteria. These compounds are termed lantibiotics because they contain the thioether amino acids lanthionine and/or methyllanthionine, in addition to 2,3-didehydroalanine and (Z)-2,3-didehydrobutyrine, which arise from enzyme catalyzed post-translational modifications. These non-proteinogenic amino acids are introduced by the dehydration of serine and threonine residues followed by stereoselective intramolecular Michael addition of cysteines onto the unsaturated amino acids. Lacticin 481 synthetase (LctM) catalyzes the post-translational modifications required for the generation of the lantibiotic lacticin 481. Recent studies of this protein responsible for the creation of the intricate polycyclic antimicrobial agent have revealed relaxed substrate specificity. In an effort to utilize this bifunctional enzyme for the engineering of novel therapeutic peptides, further substrate specificity is examined.