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Combinatorial biosynthesis in yeast leads to over 200 diterpenoids.
Frey, Maximilian; Bathe, Ulschan; Meink, Luca; Balcke, Gerd U; Schmidt, Jürgen; Frolov, Andrej; Soboleva, Alena; Hassanin, Ahmed; Davari, Mehdi D; Frank, Oliver; Schlagbauer, Verena; Dawid, Corinna; Tissier, Alain.
Afiliación
  • Frey M; Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Bathe U; Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany; Department of Horticultural Sciences, University of Florida, 2550 Hull Road, Gainesville, FL 32611, USA.
  • Meink L; Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Balcke GU; Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Schmidt J; Department of Bioorganic Chemistry Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Frolov A; Department of Bioorganic Chemistry Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Soboleva A; Department of Bioorganic Chemistry Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Hassanin A; Department of Bioorganic Chemistry Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
  • Davari MD; Department of Bioorganic Chemistry Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany.
  • Frank O; Food Chemistry and Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Straße 34, 85354 Freising, Germany.
  • Schlagbauer V; Food Chemistry and Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Straße 34, 85354 Freising, Germany.
  • Dawid C; Food Chemistry and Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Straße 34, 85354 Freising, Germany.
  • Tissier A; Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany; Martin-Luther University Halle-Wittenberg, Institute of Pharmacy, Kurt-Mothes-Strasse 3, 06120 Halle, Germany. Electronic address: alain.tissier@ipb-halle.de.
Metab Eng ; 82: 193-200, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38387676
ABSTRACT
Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases producing (+)-copalyl diphosphate-derived backbones and four cytochrome P450 oxygenases (CYPs) in diverse combinations. This resulted in the production of over 200 diterpenoids. Based on literature and chemical database searches, 162 of these compounds can be considered new-to-Nature. The CYPs accepted most substrates they were given but remained regioselective with few exceptions. Our results provide the basis for the systematic exploration of the diterpenoid chemical space in yeast using sequence databases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / Diterpenos Idioma: En Revista: Metab Eng Asunto de la revista: ENGENHARIA BIOMEDICA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Bélgica
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / Diterpenos Idioma: En Revista: Metab Eng Asunto de la revista: ENGENHARIA BIOMEDICA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Bélgica