The Leader Peptide Is Not Required for Post-Translational Modification by Lacticin 481 Synthetase

• Published in: Journal of the American Chemical Society Vol. 129; no. 34; pp. 10314 - 10315
• Main Authors: Levengood, Matthew R, Patton, Gregory C, van der Donk, Wilfred A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 29.08.2007
• Subjects: Bacteriocins - biosynthesis; Molecular Sequence Data; Protein Processing, Post-Translational; Protein Sorting Signals; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 0002-7863; 1272-7863; 1520-5126
• DOI: 10.1021/ja072967+

Lantibiotics are post-translationally modified antimicrobial peptides. The modification process features dehydration of Ser and Thr residues to the corresponding dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues and the subsequent conjugate addition by cysteine thiols onto the dehydro amino acids. The ribosomally synthesized peptide precursors contain an N-terminal leader peptide that is not modified during maturation and a C-terminal structural region that is transformed into the lantibiotic. The role of the leader peptide has been the subject of much speculation. Incubation of lacticin 481 synthetase with the structural peptide (with the leader peptide provided in trans) resulted in three of four dehydrations showing that a covalent link between the leader peptide and the structural region is not required. Incubation of lacticin 481 synthetase with the structural peptide in the absence of the leader peptide still resulted in dehydration, although the activity was reduced. These findings show that the leader peptide is not absolutely required for dehydration.