Abstract
The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway. We have completed a chromosome-level genome of Taxus chinensis var. mairei with a total length of 10.23 gigabases. Taxus shared an ancestral whole-genome duplication with the coniferophyte lineage and underwent distinct transposon evolution. We discovered a unique physical and functional grouping of CYP725As (cytochrome P450) in the Taxus genome for paclitaxel biosynthesis. We also identified a gene cluster for taxadiene biosynthesis, which was formed mainly by gene duplications. This study will facilitate the elucidation of paclitaxel biosynthesis and unleash the biotechnological potential of Taxus.
Highlights
The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway
K-mer analysis showed that the genome size of T. chinensis var. mairei was approximately 10 Gb (Extended Data Fig. 1a), which is consistent with the results
Considering that all the previously defined CYP450 genes in the paclitaxel pathway belong to the CYP725A subfamily, these results suggest that the expansion of the CYP725A subfamily played vital roles in the evolution of paclitaxel biosynthesis in Taxus
Summary
The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway. We have completed a chromosome-level genome of Taxus chinensis var. We discovered a unique physical and functional grouping of CYP725As (cytochrome P450) in the Taxus genome for paclitaxel biosynthesis. This study will facilitate the elucidation of paclitaxel biosynthesis and unleash the biotechnological potential of Taxus. Taxus is the largest genus in Taxaceae, including common species such as T. chinensis, T. brevifolia and T. baccata, and it is mainly distributed in Asia, North America and Europe[2]. Multiple strategies have been employed to address supply issues[4], and promising progress has been made in chemical[5] and semichemical synthesis[6], direct extraction from Taxus cell lines[7], fermentation of endophytic paclitaxel-producing fungi[8] and metabolic engineering of paclitaxel production using heterologous systems[9]. The paclitaxel pathway starts with geranylgeranyl diphosphate (GGPP) synthesis through the condensation of isoprenyl diphosphate and dimethylallyl diphosphate[11]
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