1 Ocak 2023 Dergi makalesi Açık Erişim

Dedeakayogullari, Huri; Valjakka, Jarkko; Turunen, Ossi; Yilmazer, Berin; Demir, Garip; Janis, Janne; Binay, Baris

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{
  "@context": "https://schema.org/", 
  "@id": 269894, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "affiliation": "Istinye Univ, Fac Med, Med Biochem Dept, TR-34010 Istanbul, Turkiye", 
      "name": "Dedeakayogullari, Huri"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Tampere Univ, Fac Med & Hlth Technol, FI-33100 Tampere, Finland", 
      "name": "Valjakka, Jarkko"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Eastern Finland, Sch Forest Sci, FI-80101 Joensuu, Finland", 
      "name": "Turunen, Ossi"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Gebze Tech Univ, Dept Mol Biol & Genet, TR-41400 Gebze, Kocaeli, Turkiye", 
      "name": "Yilmazer, Berin"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Gebze Tech Univ, Dept Mol Biol & Genet, TR-41400 Gebze, Kocaeli, Turkiye", 
      "name": "Demir, Garip"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Eastern Finland, Dept Chem, FI-80101 Joensuu, Finland", 
      "name": "Janis, Janne"
    }, 
    {
      "@type": "Person", 
      "name": "Binay, Baris"
    }
  ], 
  "datePublished": "2023-01-01", 
  "description": "<p>Unnatural amino acids are unique building blocks in modern medicinal chemistry as they contain an amino and a carboxylic acid functional group, and a variable side chain. Synthesis of pure unnatural amino acids can be made through chemical modification of natural amino acids or by employing enzymes that can lead to novel molecules used in the manufacture of various pharmaceuticals. The NAD+ -dependent alanine dehydrogenase (AlaDH) enzyme catalyzes the conversion of pyruvate to L-alanine by transferring ammonium in a reversible reductive amination activity. Although AlaDH enzymes have been widely studied in terms of oxidative deamination activity, reductive amination activity studies have been limited to the use of pyruvate as a substrate. The reductive amination potential of heterologously expressed, highly pure Thermomicrobium roseum alanine dehydrogenase (TrAlaDH) was examined with regard to pyruvate, a-ketobutyrate, a-ketovalerate and a-ketocaproate. The biochemical properties were studied, which included the effects of 11 metal ions on enzymatic activity for both reactions. The enzyme accepted both derivatives of L-alanine (in oxidative deamination) and pyruvate (in reductive amination) as substrates. While the kinetic KM values associated with the pyruvate derivatives were similar to pyruvate values, the kinetic k(cat) values were significantly affected by the side chain increase. In contrast, K-M values associated with the derivatives of L-alanine (L-a-aminobutyrate, L-norvaline, and L-norleucine) were approximately two orders of magnitude greater, which would indicate that they bind very poorly in a reactive way to the active site. The modeled enzyme structure revealed differences in the molecular orientation between L-alanine/pyruvate and L-norleucine/a-ketocaproate. The reductive activity observed would indicate that TrAlaDH has potential for the synthesis of pharmaceutically relevant amino acids.</p>", 
  "headline": "Application of reductive amination by heterologously expressed <i>Thermomicrobium roseum</i> L-alanine dehydrogenase to synthesize L-alanine derivatives", 
  "identifier": 269894, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "Application of reductive amination by heterologously expressed <i>Thermomicrobium roseum</i> L-alanine dehydrogenase to synthesize L-alanine derivatives", 
  "url": "https://aperta.ulakbim.gov.tr/record/269894"
}