Abstract
Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps. Here, we report chromosome-level reference and phased genome assembly of Ophiorrhiza pumila, a camptothecin-producing medicinal plant, through an ordered multi-scaffolding and experimental validation approach. With 21 assembly gaps and a contig N50 of 18.49 Mb, Ophiorrhiza genome is one of the most complete plant genomes assembled to date. We also report 273 nitrogen-containing metabolites, including diverse monoterpene indole alkaloids (MIAs). A comparative genomics approach identifies strictosidine biogenesis as the origin of MIA evolution. The emergence of strictosidine biosynthesis-catalyzing enzymes precede downstream enzymes’ evolution post γ whole-genome triplication, which occurred approximately 110 Mya in O. pumila, and before the whole-genome duplication in Camptotheca acuminata identified here. Combining comparative genome analysis, multi-omics analysis, and metabolic gene-cluster analysis, we propose a working model for MIA evolution, and a pangenome for MIA biosynthesis, which will help in establishing a sustainable supply of camptothecin.
Highlights
Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps
Using OrthoFinder-based gene classification, we identified a total of 15,943 orthogroups shared among the four monoterpene indole alkaloids (MIAs)-producing plants, with 64.8% of orthogroups being common to all four species and 513 orthogroups being specific to the MIA-producing plants (Supplementary Fig. 28 and Supplementary Data 20)
Among Gentianales, the emergence of STR for the synthesis of strictosidine was an important innovation to promote the evolution of MIA biosynthesis, which occurred after the whole-genome triplication of core eudicot genomes (Fig. 6e and Supplementary Fig. 41)
Summary
Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps. We report chromosome-level reference and phased genome assembly of Ophiorrhiza pumila, a camptothecin-producing medicinal plant, through an ordered multi-scaffolding and experimental validation approach. Most of our current understanding of MIA biosynthesis is restricted to the vinca alkaloid synthesis pathway elucidated in Catharanthus roseus[4,5,6,7,8,9] Camptothecin, another strictosidinederived molecule and one of the most potent anticancer MIAs, is the precursor for the commercial synthesis of topotecan and irinotecan, and several other camptothecin derivatives are in clinical trials at different stages[10,11]. We show the advantage of ordered multitiered scaffolding with assembly validation at each stage to achieve a highly contiguous genome assembly This strategy allows us to derive a near-finished and experimentally validated reference and phased genome assembly of O. pumila. This study, by establishing a high-quality genome and metabolome resource for O. pumila, provides a foundation for yield improvement of valuable anticancer metabolites through synthetic biology and biotechnology
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