Document Detail

Investigation of the substrate specificity of lacticin 481 synthetase by using nonproteinogenic amino acids.
MedLine Citation:
PMID:  19222036     Owner:  NLM     Status:  MEDLINE    
Lantibiotics are peptide antimicrobial compounds that are characterized by the thioether-bridged amino acids lanthionine and methyllanthionine. For lacticin 481, these structures are installed in a two-step post-translational modification process by a bifunctional enzyme, lacticin 481 synthetase (LctM). LctM catalyzes the dehydration of Ser and Thr residues to generate dehydroalanine or dehydrobutyrine, respectively, and the subsequent intramolecular regio- and stereospecific Michael-type addition of cysteines onto the dehydroamino acids. In this study, semisynthetic substrates containing nonproteinogenic amino acids were prepared by expressed protein ligation and [3+2]-cycloaddition of azide and alkyne-functionalized peptides. LctM demonstrated broad substrate specificity toward substrates containing beta-amino acids, D-amino acids, and N-alkyl amino acids (peptoids) in certain regions of its peptide substrate. These findings showcase its promise for use in lantibiotic and peptide-engineering applications, whereby nonproteinogenic amino acids might impart improved stability or modulated biological activities. Furthermore, LctM permitted the incorporation of an alkyne-containing amino acid that can be utilized for the site-selective modification of mature lantibiotics and used in target identification.
Matthew R Levengood; Christopher C Kerwood; Champak Chatterjee; Wilfred A van der Donk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chembiochem : a European journal of chemical biology     Volume:  10     ISSN:  1439-7633     ISO Abbreviation:  Chembiochem     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-30     Completed Date:  2009-06-08     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  100937360     Medline TA:  Chembiochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  911-9     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Amino Acids / chemistry,  metabolism*
Anti-Bacterial Agents / metabolism*
Bacteriocins / metabolism*
Enzymes / metabolism*
Molecular Sequence Data
Molecular Structure
Peptides / chemistry,  genetics,  metabolism
Protein Processing, Post-Translational
Sequence Alignment
Substrate Specificity
Grant Support
GM58822/GM/NIGMS NIH HHS; R01 GM058822/GM/NIGMS NIH HHS; R01 GM058822-09/GM/NIGMS NIH HHS; T32 GM008276/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Amino Acids; 0/Anti-Bacterial Agents; 0/Bacteriocins; 0/Enzymes; 0/LctM protein, Lactococcus lactis; 0/Peptides; 136959-47-2/lacticin 481

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