Deuterium labeled peptides give insights into the directionality of class III lantibiotic synthetase LabKC.

Abstract

The biosynthesis of a considerable number of ribosomally synthesized peptide antibiotics involves the modification of Ser and Thr residues of a precursor peptide. This post-translational processing is performed by one or multiple modifying enzymes encoded in the biosynthetic gene cluster. We present a deuterium-label based enzyme assay, utilizing a series of peptide substrates with α-deuterated Ser, for the determination of the dehydration order during the biosynthesis of class III lantibiotic labyrinthopeptin A2. Remarkably, the data show that, in contrast to other modifying enzymes of class I and II lantibiotics, LabKC has a C- to N-terminal processing mode. This surprising finding, which we consider relevant for the biosyntheses of other class III lantibiotics, underlines significant differences of this class of modifying enzymes compared to other investigated systems.

• Authors: Bartlomiej Krawczyk, Paul Ensle, Wolfgang M Müller, Roderich D Süssmuth
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 134 Issue 24 Pg. 9922-5 (Jun 20 2012) ISSN: 1520-5126 [Electronic] United States
• PMID: 22687055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Bacteriocins
• Peptides
• labyrinthopeptin A2
• Serine
• Deuterium
• Ligases

Topics

• Amino Acid Sequence
• Anti-Bacterial Agents (chemistry, metabolism)
• Bacteria (chemistry, enzymology, metabolism)
• Bacteriocins (chemistry, metabolism)
• Deuterium (chemistry, metabolism)
• Enzyme Assays (methods)
• Ligases (chemistry, metabolism)
• Molecular Sequence Data
• Peptides (chemistry, metabolism)
• Serine (chemistry, metabolism)