Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis

نویسندگان

  • Johan Andersen-Ranberg
  • Kenneth Thermann Kongstad
  • Morten Thrane Nielsen
  • Niels Bjerg Jensen
  • Irini Pateraki
  • Søren Spanner Bach
  • Britta Hamberger
  • Philipp Zerbe
  • Dan Staerk
  • Jörg Bohlmann
  • Birger Lindberg Møller
  • Björn Hamberger
چکیده

Plant-derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are "new-to-nature". Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.

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عنوان ژورنال:

دوره 55  شماره 

صفحات  -

تاریخ انتشار 2016