Large-scale mining of plant genomes unlocks the diversity of oxidosqualene cyclases

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Abstract
The differential cyclization and rearrangement of 2,3-oxidosqualene controlled by oxidosqualene cyclases (OSCs) represents one of the most complex single enzyme transformations in nature and gives rise to a vast array of triterpenoid diversity in the plant kingdom. Here we systematically mine 599 plant genomes representing 387 species and investigate OSC diversity across different plant lineages. From the OSC sequences identified, 20 were selected for functional evaluation. Through analysis of these enzymes, we discover product profiles within clades previously believed to be functionally conserved and OSCs producing triterpenes for which no enzymatic source was known. We also discover OSCs with product profiles that yield mechanistic insights into the control of specific reaction pathways. Our study reveals lineage-specific blooms of OSC subgroups suggestive of adaptation to different environmental niches, opens up previously inaccessible chemistry and provides a framework for systematic investigations of metabolic diversification and underlying enzymatic mechanisms in the plant kingdom.
Funding Information
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/L014130/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/S016023/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/X01097X/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/L014130/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/S016023/1)
  • Novo Nordisk Fonden (NNF23SA0084012)
  • Wellcome Trust (227375/Z/23/Z)
  • John Innes Foundation (-)
  • John Innes Foundation (-)
  • U.S. Department of Health & Human Services | National Institutes of Health (1R01AT010593-01)
  • U.S. Department of Health & Human Services | National Institutes of Health (1R01AT010593-01)

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