Novel L-amino acid ligases catalyzing oligopeptide synthesis

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    L-Amino acid ligase (EC 6.3.2.28) is a microbial enzyme catalyzing formation of an alpha-peptide bond from unprotected L-amino acids in an ATP-dependent manner. The YwfE protein from Bacillus subtilis 168 was the first reported L-amino acid ligase, and it synthesizes various dipeptides. Thereafter, several L-amino acid ligases were newly obtained by in silico analysis using the ATP-grasp motif. But these L-amino acid ligases synthesize only dipeptide and no longer peptide. A novel L-amino acid ligase capable of catalyzing oligopeptide synthesis is required to increase the variety of peptides. We have previously found a new member of L-amino acid ligase, RizA, from B. subtilis NBRC3134, a microorganism that produces the peptide-antibiotic rhizocticin. We newly found that a gene at approximately 9 kbp upstream of rizA encoded a novel L-amino acid ligase RizB. Recombinant RizB synthesized homo-oligomers of branched-chain amino acids consisting of 2 to 5 amino acids, and also synthesized various heteropeptides. RizB is the first reported L-amino acid ligase that catalyzes oligopeptide synthesis. In addition, we obtained L-amino acid ligases showing oligopeptide synthesis activities by in silico analysis using BLAST, which is a set of similarity search programs. These L-amino acid ligases showed low similarity in amino acid sequence, but commonly used branched-chain amino acids, such as RizB, as substrates. Furthermore, the spr0969 protein of Streptococcus pneumoniae synthesized longer peptides than those synthesized by RizB, and the BAD-1200 protein of Bifidobacteria adolescentis showed higher activity toward aromatic amino acids than toward branched-chain ones.

    Original languageEnglish
    Pages (from-to)1463-1469
    Number of pages7
    JournalYakugaku Zasshi
    Volume130
    Issue number11
    DOIs
    Publication statusPublished - 2010 Nov

    Fingerprint

    Oligopeptides
    Ligases
    Amino Acids
    Peptides
    Branched Chain Amino Acids
    Dipeptides
    Bacillus subtilis
    Computer Simulation
    Adenosine Triphosphate
    Aromatic Amino Acids
    Proteins
    Hand Strength
    Streptococcus pneumoniae
    Amino Acid Sequence

    Keywords

    • In silico analysis
    • L-amino acid ligase
    • Oligopeptide synthesis
    • Rhizocticin

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmaceutical Science

    Cite this

    Novel L-amino acid ligases catalyzing oligopeptide synthesis. / Kino, Kuniki.

    In: Yakugaku Zasshi, Vol. 130, No. 11, 11.2010, p. 1463-1469.

    Research output: Contribution to journalArticle

    @article{0122c6885d2a4d83bea9fc604eb042a6,
    title = "Novel L-amino acid ligases catalyzing oligopeptide synthesis",
    abstract = "L-Amino acid ligase (EC 6.3.2.28) is a microbial enzyme catalyzing formation of an alpha-peptide bond from unprotected L-amino acids in an ATP-dependent manner. The YwfE protein from Bacillus subtilis 168 was the first reported L-amino acid ligase, and it synthesizes various dipeptides. Thereafter, several L-amino acid ligases were newly obtained by in silico analysis using the ATP-grasp motif. But these L-amino acid ligases synthesize only dipeptide and no longer peptide. A novel L-amino acid ligase capable of catalyzing oligopeptide synthesis is required to increase the variety of peptides. We have previously found a new member of L-amino acid ligase, RizA, from B. subtilis NBRC3134, a microorganism that produces the peptide-antibiotic rhizocticin. We newly found that a gene at approximately 9 kbp upstream of rizA encoded a novel L-amino acid ligase RizB. Recombinant RizB synthesized homo-oligomers of branched-chain amino acids consisting of 2 to 5 amino acids, and also synthesized various heteropeptides. RizB is the first reported L-amino acid ligase that catalyzes oligopeptide synthesis. In addition, we obtained L-amino acid ligases showing oligopeptide synthesis activities by in silico analysis using BLAST, which is a set of similarity search programs. These L-amino acid ligases showed low similarity in amino acid sequence, but commonly used branched-chain amino acids, such as RizB, as substrates. Furthermore, the spr0969 protein of Streptococcus pneumoniae synthesized longer peptides than those synthesized by RizB, and the BAD-1200 protein of Bifidobacteria adolescentis showed higher activity toward aromatic amino acids than toward branched-chain ones.",
    keywords = "In silico analysis, L-amino acid ligase, Oligopeptide synthesis, Rhizocticin",
    author = "Kuniki Kino",
    year = "2010",
    month = "11",
    doi = "10.1248/yakushi.130.1463",
    language = "English",
    volume = "130",
    pages = "1463--1469",
    journal = "Yakugaku Zasshi",
    issn = "0031-6903",
    publisher = "Pharmaceutical Society of Japan",
    number = "11",

    }

    TY - JOUR

    T1 - Novel L-amino acid ligases catalyzing oligopeptide synthesis

    AU - Kino, Kuniki

    PY - 2010/11

    Y1 - 2010/11

    N2 - L-Amino acid ligase (EC 6.3.2.28) is a microbial enzyme catalyzing formation of an alpha-peptide bond from unprotected L-amino acids in an ATP-dependent manner. The YwfE protein from Bacillus subtilis 168 was the first reported L-amino acid ligase, and it synthesizes various dipeptides. Thereafter, several L-amino acid ligases were newly obtained by in silico analysis using the ATP-grasp motif. But these L-amino acid ligases synthesize only dipeptide and no longer peptide. A novel L-amino acid ligase capable of catalyzing oligopeptide synthesis is required to increase the variety of peptides. We have previously found a new member of L-amino acid ligase, RizA, from B. subtilis NBRC3134, a microorganism that produces the peptide-antibiotic rhizocticin. We newly found that a gene at approximately 9 kbp upstream of rizA encoded a novel L-amino acid ligase RizB. Recombinant RizB synthesized homo-oligomers of branched-chain amino acids consisting of 2 to 5 amino acids, and also synthesized various heteropeptides. RizB is the first reported L-amino acid ligase that catalyzes oligopeptide synthesis. In addition, we obtained L-amino acid ligases showing oligopeptide synthesis activities by in silico analysis using BLAST, which is a set of similarity search programs. These L-amino acid ligases showed low similarity in amino acid sequence, but commonly used branched-chain amino acids, such as RizB, as substrates. Furthermore, the spr0969 protein of Streptococcus pneumoniae synthesized longer peptides than those synthesized by RizB, and the BAD-1200 protein of Bifidobacteria adolescentis showed higher activity toward aromatic amino acids than toward branched-chain ones.

    AB - L-Amino acid ligase (EC 6.3.2.28) is a microbial enzyme catalyzing formation of an alpha-peptide bond from unprotected L-amino acids in an ATP-dependent manner. The YwfE protein from Bacillus subtilis 168 was the first reported L-amino acid ligase, and it synthesizes various dipeptides. Thereafter, several L-amino acid ligases were newly obtained by in silico analysis using the ATP-grasp motif. But these L-amino acid ligases synthesize only dipeptide and no longer peptide. A novel L-amino acid ligase capable of catalyzing oligopeptide synthesis is required to increase the variety of peptides. We have previously found a new member of L-amino acid ligase, RizA, from B. subtilis NBRC3134, a microorganism that produces the peptide-antibiotic rhizocticin. We newly found that a gene at approximately 9 kbp upstream of rizA encoded a novel L-amino acid ligase RizB. Recombinant RizB synthesized homo-oligomers of branched-chain amino acids consisting of 2 to 5 amino acids, and also synthesized various heteropeptides. RizB is the first reported L-amino acid ligase that catalyzes oligopeptide synthesis. In addition, we obtained L-amino acid ligases showing oligopeptide synthesis activities by in silico analysis using BLAST, which is a set of similarity search programs. These L-amino acid ligases showed low similarity in amino acid sequence, but commonly used branched-chain amino acids, such as RizB, as substrates. Furthermore, the spr0969 protein of Streptococcus pneumoniae synthesized longer peptides than those synthesized by RizB, and the BAD-1200 protein of Bifidobacteria adolescentis showed higher activity toward aromatic amino acids than toward branched-chain ones.

    KW - In silico analysis

    KW - L-amino acid ligase

    KW - Oligopeptide synthesis

    KW - Rhizocticin

    UR - http://www.scopus.com/inward/record.url?scp=78349235121&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=78349235121&partnerID=8YFLogxK

    U2 - 10.1248/yakushi.130.1463

    DO - 10.1248/yakushi.130.1463

    M3 - Article

    C2 - 21048404

    AN - SCOPUS:78349235121

    VL - 130

    SP - 1463

    EP - 1469

    JO - Yakugaku Zasshi

    JF - Yakugaku Zasshi

    SN - 0031-6903

    IS - 11

    ER -