Introduction of a Non-Natural Amino Acid into a Nonribosomal Peptide Antibiotic by Modification of Adenylation Domain Specificity

This highlight focuses on one of Nature's key strategies to doubly modify an amino acid during nonribosomal peptide biosynthesis by using a single enzyme, an interrupted adenylation domain.

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Structure of a Eukaryotic Nonribosomal Peptide Synthetase Adenylation Domain That Activates a Large Hydroxamate Amino Acid in Siderophore Biosynthesis

Journal of Biological Chemistry ◽

10.1074/jbc.m109.071324 ◽

2009 ◽

Vol 285 (4) ◽

pp. 2415-2427 ◽

Cited By ~ 40

Author(s):

T. Verne Lee ◽

Linda J. Johnson ◽

Richard D. Johnson ◽

Albert Koulman ◽

Geoffrey A. Lane ◽

...

Keyword(s):

Amino Acid ◽

Nonribosomal Peptide Synthetase ◽

Adenylation Domain ◽

Nonribosomal Peptide ◽

Siderophore Biosynthesis ◽

Peptide Synthetase

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CORTICOTROPHIC EFFECT OF SYNTHETIC ACTH-PEPTIDES WITH NATURAL AMINO ACID SEQUENCE OF DIFFERENT CHAIN LENGTH IN COMPARISON TO THEIR D-SER1-DERIVATIVES

Acta Endocrinologica ◽

10.1530/acta.0.067s048 ◽

1971 ◽

Vol 68 (1_Supplb) ◽

pp. S48

Author(s):

P. L. Barthe ◽

L. Schenkel-Hulliger ◽

W. Rittel ◽

P. A. Desaulles

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Chain Length ◽

Natural Amino Acid

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Faculty Opinions recommendation of Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11466956.14747140 ◽

2011 ◽

Author(s):

Francis Tsai ◽

Amadeo Biter

Keyword(s):

Amino Acid ◽

Amyloid Fibril ◽

Fibril Formation ◽

Natural Amino Acid ◽

Amyloid Fibril Formation

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Beneficial Impacts of Incorporating the Non-Natural Amino Acid Azulenyl-Alanine into the Trp-Rich Antimicrobial Peptide buCATHL4B

Biomolecules ◽

10.3390/biom11030421 ◽

2021 ◽

Vol 11 (3) ◽

pp. 421

Author(s):

Areetha R. D’Souza ◽

Matthew R. Necelis ◽

Alona Kulesha ◽

Gregory A. Caputo ◽

Olga V. Makhlynets

Keyword(s):

Amino Acid ◽

Antimicrobial Peptides ◽

Antimicrobial Peptide ◽

Mechanism Of Action ◽

Bactericidal Activity ◽

Antimicrobial Agents ◽

Human Cells ◽

Side Chains ◽

Natural Amino Acid ◽

Proteolytic Stability

Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.

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