Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis

• Published in: Nature communications Vol. 12; no. 1; p. 405
• Main Authors: Rai, Amit, Hirakawa, Hideki, Nakabayashi, Ryo, Kikuchi, Shinji, Hayashi, Koki, Rai, Megha, Tsugawa, Hiroshi, Nakaya, Taiki, Mori, Tetsuya, Nagasaki, Hideki, Fukushi, Runa, Kusuya, Yoko, Takahashi, Hiroki, Uchiyama, Hiroshi, Toyoda, Atsushi, Hikosaka, Shoko, Goto, Eiji, Saito, Kazuki, Yamazaki, Mami
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-01-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 140/58; 38/22; 38/32; 38/39; 45/23; 631/449/2491; 631/449/2667; 631/449/2669; 631/449/447; 631/61/320; Alkaloids; Assembly; Biosynthesis; Biosynthetic Pathways - genetics; Camptothecin; Camptothecin - biosynthesis; Chromosomes; Chromosomes, Plant - genetics; Cluster analysis; Contig Mapping; Enzymes; Evolution; Evolution, Molecular; Genome, Plant - genetics; Genomes; Genomics; Herbal medicine; Humanities and Social Sciences; Indoles; Medicinal plants; Metabolism; Metabolites; multidisciplinary; Plant Proteins - genetics; Plant Proteins - metabolism; Plant Roots - metabolism; Plants, Medicinal - genetics; Plants, Medicinal - metabolism; Rubiaceae - genetics; Rubiaceae - metabolism; Scaffolding; Science; Science (multidisciplinary); Synteny; Vinca Alkaloids - biosynthesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20508-2

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.
Ophiorrhiza pumila
is a medicinal plant that can produce the anti-cancer monoterpene indole alkaloid (MIA) camptothecin. Here, the authors report its genome assembly and propose a working model for MIA evolution and biosynthesis through comparative genomics, synteny, and metabolic gene cluster analyses.