IRIS publication 160754172
Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147
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TY - JOUR - Cotter, PD,O'Connor, PM,Draper, LA,Lawton, EM,Deegan, LH,Hill, C,Ross, RP - 2005 - February - 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 - () - antimicrobial bacteriocin chirality 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). - DOI 10.1073/pnas.0509371102 DA - 2005/02 ER -
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@article{V160754172, = {Cotter, PD and O'Connor, PM and Draper, LA and Lawton, EM and Deegan, LH and Hill, C and Ross, RP }, = {2005}, = {February}, = {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}, = {()}, = {antimicrobial bacteriocin chirality D-AMINO-ACID LACTOCOCCUS-LACTIS ANTIMICROBIAL ACTIVITY NUCLEOTIDE-SEQUENCE PEPTIDE PLASMID DIASTEREOMERS MELITTIN SYSTEM BACTERIOCINS}, = {102}, pages = {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).}}, = {DOI 10.1073/pnas.0509371102}, source = {IRIS} }
Data as stored in IRIS
AUTHORS | Cotter, PD,O'Connor, PM,Draper, LA,Lawton, EM,Deegan, LH,Hill, C,Ross, RP | ||
YEAR | 2005 | ||
MONTH | February | ||
JOURNAL_CODE | Proceedings of The National Academy of Sciences of The United States of America | ||
TITLE | Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147 | ||
STATUS | Validated | ||
TIMES_CITED | () | ||
SEARCH_KEYWORD | antimicrobial bacteriocin chirality D-AMINO-ACID LACTOCOCCUS-LACTIS ANTIMICROBIAL ACTIVITY NUCLEOTIDE-SEQUENCE PEPTIDE PLASMID DIASTEREOMERS MELITTIN SYSTEM BACTERIOCINS | ||
VOLUME | 102 | ||
ISSUE | |||
START_PAGE | 18584 | ||
END_PAGE | 18589 | ||
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 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). | ||
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DOI_LINK | DOI 10.1073/pnas.0509371102 | ||
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