Type

Journal Article

Authors

R Paul Ross
Colin Hill
Lucy H Deegan
Elaine M. Lawton
Lorraine A Draper
Paula M. O'Connor
Paul D. Cotter

Subjects

Biochemistry

Topics
threonine serine alanine lactococcus lactis bacteriocins molecular sequence data structure activity relationship valine codon protein processing post translational chemistry amino acid sequence chromatography high pressure liquid glycine enzymology genetics lacticin 481 metabolism

Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147. (2005)

Abstract As a general rule, ribosomally synthesized polypeptides contain amino acids only in the L-isoform in an order dictated by the coding DNA/RNA. Two of a total of only four examples of L to D conversions in prokaryotic systems occur in posttranslationally modified antimicrobial peptides called lantibiotics. In both examples (lactocin S and lacticin 3147), ribosomally encoded L-serines are enzymatically converted to D-alanines, giving rise to an apparent mistranslation of serine codons to alanine residues. It has been suggested that this conversion results from a two-step reaction initiated by a lantibiotic synthetase converting the gene-encoded L-serine to dehydroalanine (dha). By using lacticin 3147 as a model system, we report the identification of an enzyme, LtnJ, that is responsible for the conversion of dha to D-alanine. Deletion of this enzyme results in the residues remaining as dha intermediates, leading to a dramatic reduction in the antimicrobial activity of the producing strain. The importance of the chirality of the three D-alanines present in lacticin 3147 was confirmed when these residues were systematically substituted by L-alanines. In addition, substitution with L-threonine (ultimately modified to dehydrobutyrine), glycine, or L-valine also resulted in diminished peptide production and/or relative activity, the extent of which depended on the chirality of the newly incorporated amino acid(s).
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

R Paul Ross, Colin Hill, Lucy H Deegan, Elaine M. Lawton, Lorraine A Draper, Paula M. O'Connor, Paul D. Cotter

Experts in our system

1
R Paul Ross
Teagasc
Total Publications: 441
 
2
Colin Hill
University College Cork
Total Publications: 351
 
3
Elaine M. Lawton
University College Cork
Total Publications: 12
 
4
Lorraine A Draper
University College Cork
Total Publications: 24
 
5
Paula M. O'Connor
Teagasc
Total Publications: 85
 
6
Paul D. Cotter
Teagasc
Total Publications: 253