Synthesis of D-amino acid-containing dipeptides using the adenylation domains of nonribosomal peptide synthetase

Soichiro Kano, Shin Suzuki, Ryotaro Hara, Kuniki Kino

Research output: Contribution to journalArticle

Abstract

Recent papers have reported dipeptides containing D-amino acids to have novel effects that cannot be observed with LL-dipeptides, and such dipeptides are expected to be novel functional compounds for pharmaceuticals and food additives. Although the functions of D-amino acid-containing dipeptides are gaining more attention, there are few reports on the synthetic enzymes that can accept D-amino acids as substrates, and synthetic methods for D-amino acid-containing dipeptides have not yet been constructed. Previously, we developed a chemoenzymatic system for amide synthesis that comprised enzymatic activation and a subsequent nucleophilic substitution reaction. In this study, we demonstrated the application of the system for D-amino acid-containing-dipeptide synthesis. We chose six adenylation domains as targets according to our newly constructed hypothesis, i.e., an adenylation domain located upstream from the epimerization domain may activate D-amino acid as well as L-amino acid. We successfully synthesized over 40 kinds of D-amino acid-containing dipeptides, including LD-, DL-, and DD-dipeptides, using only two adenylation domains, TycA-A from tyrocidine synthetase and BacB2-A from bacitracin synthetase. Furthermore, this study offered the possibility that the epimerization domain could be a clue to the activity of the adenylation domains toward D-amino acid. This paper provides additional information regarding D-amino acid-containing-dipeptide synthesis through the combination of enzymatic adenylation and chemical nucleophilic reaction, and this system will be a useful tool for dipeptide synthesis.

Original languageEnglish
Article numbere00120-19
JournalApplied and Environmental Microbiology
Volume85
Issue number13
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Peptide Synthases
dipeptides
Dipeptides
ligases
peptide
amino acid
peptides
Amino Acids
amino acids
synthesis
tyrocidine
bacitracin
Food Additives
food additives
chemical reactions
amides
Amides
chemical reaction
substitution
drug

Keywords

  • Adenylation domain
  • D-amino acid
  • Dipeptide synthesis
  • Nonribosomal peptide synthetase

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Applied Microbiology and Biotechnology
  • Ecology

Cite this

Synthesis of D-amino acid-containing dipeptides using the adenylation domains of nonribosomal peptide synthetase. / Kano, Soichiro; Suzuki, Shin; Hara, Ryotaro; Kino, Kuniki.

In: Applied and Environmental Microbiology, Vol. 85, No. 13, e00120-19, 01.01.2019.

Research output: Contribution to journalArticle

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