Peer-Reviewed Journal Details
Mandatory Fields
Cotter, PD;O'Connor, PM;Draper, LA;Lawton, EM;Deegan, LH;Hill, C;Ross, RP
2005
December
Proceedings of The National Academy of Sciences of The United States of America
Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147
Validated
WOS: 107 ()
Optional Fields
D-AMINO-ACID LACTOCOCCUS-LACTIS ANTIMICROBIAL ACTIVITY NUCLEOTIDE-SEQUENCE PEPTIDE PLASMID DIASTEREOMERS MELITTIN SYSTEM BACTERIOCINS
102
18584
18589
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 clehydroalanine (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 weir 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).
WASHINGTON
0027-8424
10.1073/pnas.0509371102
Grant Details