Investigation of the Substrate Specificity of Lacticin 481 Synthetase by Using Nonproteinogenic Amino Acids
| Autor: | Wilfred A. van der Donk, Champak Chatterjee, Christopher C. Kerwood, Matthew R. Levengood |
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| Rok vydání: | 2009 |
| Předmět: |
Stereochemistry
Molecular Sequence Data Peptide Biology Biochemistry Article Substrate Specificity chemistry.chemical_compound Bacteriocins Biosynthesis Dehydroalanine Amino Acid Sequence Amino Acids Molecular Biology Peptide sequence Lanthionine chemistry.chemical_classification Molecular Structure Organic Chemistry Lantibiotics Anti-Bacterial Agents Enzymes Amino acid chemistry Molecular Medicine Azide Peptides Protein Processing Post-Translational Sequence Alignment |
| Zdroj: | ChemBioChem. 10:911-919 |
| ISSN: | 1439-7633 1439-4227 |
| DOI: | 10.1002/cbic.200800752 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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