title: Facile Removal of Leader Peptides from Lanthipeptides by Incorporation of a Hydroxy Acid.
abstract: The biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products typically involves a precursor peptide which contains a leader peptide that is important for the modification process, and that is removed in the final step by a protease. Genome mining efforts for new RiPPs are often hampered by the lack of a general method to remove the leader peptides. We describe here the incorporation of hydroxy acids into the precursor peptides in E. coli which results in connection of the leader peptide via an ester linkage that is readily cleaved by simple hydrolysis. We demonstrate the method for two lantibiotics, lacticin 481 and nukacin ISK-1.
authors.affiliation: †Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Champaign, Illinois 61820, United States.
authors.forename: Noah A
authors.initials: NA
authors.lastname: Bindman
authors.affiliation: †Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Champaign, Illinois 61820, United States.
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Bobeica
authors.forename: Wenshe R
authors.initials: WR
authors.lastname: Liu
authors.affiliation: †Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Champaign, Illinois 61820, United States.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D006880:Hydroxy Acids / Q000737:chemistry*; D007811:Lanthanum / Q000737:chemistry*; D021382:Protein Sorting Signals; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006880:Hydroxy Acids; D021382:Protein Sorting Signals; D007811:Lanthanum