A gene cluster in Ginkgo biloba encodes unique multifunctional cytochrome P450s that initiate ginkgolide biosynthesis

The ginkgo tree ( Ginkgo biloba ) is considered a living fossil due to its 200 million year’s history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilacto...

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Published in:Nature communications 2022-09, Vol.13 (1), p.5143-5143, Article 5143
Main Authors: Forman, Victor, Luo, Dan, Geu-Flores, Fernando, Lemcke, René, Nelson, David R., Kampranis, Sotirios C., Staerk, Dan, Møller, Birger Lindberg, Pateraki, Irini
Format: Article
Language:English
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Angiosperms
Bilobalide
Biosynthesis
Covalent bonds
Cytochrome
Cytochromes
Ginkgo biloba
Ginkgolides
Gymnosperms
Humanities and Social Sciences
Living fossils
Mesozoic
Metabolites
multidisciplinary
Science
Science (multidisciplinary)
Terpenes
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Summary:The ginkgo tree ( Ginkgo biloba ) is considered a living fossil due to its 200 million year’s history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilactones. Here, we use a gene cluster-guided mining approach in combination with co-expression analysis to reveal the primary steps in ginkgolide biosynthesis. We show that five multifunctional cytochrome P450s with atypical catalytic activities generate the tert -butyl group and one of the lactone rings, characteristic of all G. biloba trilactone terpenoids. The reactions include scarless C–C bond cleavage as well as carbon skeleton rearrangement (NIH shift) occurring on a previously unsuspected intermediate. The cytochrome P450s belong to CYP families that diversifies in pre-seed plants and gymnosperms, but are not preserved in angiosperms. Our work uncovers the early ginkgolide pathway and offers a glance into the biosynthesis of terpenoids of the Mesozoic Era. Although ginkgo terpenoids have been studied extensively for their pharmaceutical properties, knowledge on their biosynthesis remains limited. Here, the authors identify five multifunctional cytochrome P450s that catalyze the generation of the tert-butyl group and one of the lactone rings towards the biosynthesis of ginkgolides.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-32879-9