Cargando…

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

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 com...

Descripción completa

Detalles Bibliográficos
Autores principales: Andersen‐Ranberg, Johan, Kongstad, Kenneth Thermann, Nielsen, Morten Thrane, Jensen, Niels Bjerg, Pateraki, Irini, Bach, Søren Spanner, Hamberger, Britta, Zerbe, Philipp, Staerk, Dan, Bohlmann, Jörg, Møller, Birger Lindberg, Hamberger, Björn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755150/
https://www.ncbi.nlm.nih.gov/pubmed/26749264
http://dx.doi.org/10.1002/anie.201510650
_version_ 1782416154253328384
author Andersen‐Ranberg, Johan
Kongstad, Kenneth Thermann
Nielsen, Morten Thrane
Jensen, Niels Bjerg
Pateraki, Irini
Bach, Søren Spanner
Hamberger, Britta
Zerbe, Philipp
Staerk, Dan
Bohlmann, Jörg
Møller, Birger Lindberg
Hamberger, Björn
author_facet Andersen‐Ranberg, Johan
Kongstad, Kenneth Thermann
Nielsen, Morten Thrane
Jensen, Niels Bjerg
Pateraki, Irini
Bach, Søren Spanner
Hamberger, Britta
Zerbe, Philipp
Staerk, Dan
Bohlmann, Jörg
Møller, Birger Lindberg
Hamberger, Björn
author_sort Andersen‐Ranberg, Johan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4755150
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-47551502016-02-25 Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis Andersen‐Ranberg, Johan Kongstad, Kenneth Thermann Nielsen, Morten Thrane Jensen, Niels Bjerg Pateraki, Irini Bach, Søren Spanner Hamberger, Britta Zerbe, Philipp Staerk, Dan Bohlmann, Jörg Møller, Birger Lindberg Hamberger, Björn Angew Chem Int Ed Engl Communications 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. John Wiley and Sons Inc. 2016-01-08 2016-02-02 /pmc/articles/PMC4755150/ /pubmed/26749264 http://dx.doi.org/10.1002/anie.201510650 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Communications
Andersen‐Ranberg, Johan
Kongstad, Kenneth Thermann
Nielsen, Morten Thrane
Jensen, Niels Bjerg
Pateraki, Irini
Bach, Søren Spanner
Hamberger, Britta
Zerbe, Philipp
Staerk, Dan
Bohlmann, Jörg
Møller, Birger Lindberg
Hamberger, Björn
Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title_full Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title_fullStr Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title_full_unstemmed Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title_short Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis
title_sort expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755150/
https://www.ncbi.nlm.nih.gov/pubmed/26749264
http://dx.doi.org/10.1002/anie.201510650
work_keys_str_mv AT andersenranbergjohan expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT kongstadkenneththermann expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT nielsenmortenthrane expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT jensennielsbjerg expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT paterakiirini expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT bachsørenspanner expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT hambergerbritta expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT zerbephilipp expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT staerkdan expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT bohlmannjorg expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT møllerbirgerlindberg expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis
AT hambergerbjorn expandingthelandscapeofditerpenestructuraldiversitythroughstereochemicallycontrolledcombinatorialbiosynthesis