Structural Analysis of Class I Lanthipeptides from Pedobacter lusitanus NL19 Reveals an Unusual Ring Pattern

• Published in: ACS chemical biology 2021-06, Vol.16 (6), p.1019-1029
• Main Authors: Bothwell, Ian R, Caetano, Tânia, Sarksian, Raymond, Mendo, Sónia, van der Donk, Wilfred A
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - chemistry; Alanine - metabolism; Amino Acid Sequence; Bacteriocins - chemistry; Bacteriocins - metabolism; Pedobacter - chemistry; Pedobacter - metabolism; Peptides - chemistry; Peptides - metabolism; Protein Processing, Post-Translational; Sulfides - chemistry; Sulfides - metabolism
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.1c00106

Lanthipeptides are ribosomally synthesized and post-translationally modified peptide natural products characterized by the presence of lanthionine and methyllanthionine cross-linked amino acids formed by dehydration of Ser/Thr residues followed by conjugate addition of Cys to the resulting dehydroamino acids. Class I lanthipeptide dehydratases utilize glutamyl-tRNAGlu as a cosubstrate to glutamylate Ser/Thr followed by glutamate elimination. A vast majority of lanthipeptides identified from class I synthase systems have been from Gram-positive bacteria. Herein, we report the heterologous expression and modification in Escherichia coli of two lanthipeptides from the Gram-negative Bacteroidetes Pedobacter lusitanus NL19. These peptides are representative of a group of compounds frequently encoded in Pedobacter genomes. Structural characterization of the lanthipeptides revealed a novel ring pattern as well as an unusual ll-lanthionine stereochemical configuration and a cyclase that lacks the canonical zinc ligands found in most LanC enzymes.