Single Cell Multi‐Omics Reveals Rare Biosynthetic Cell Types in the Medicinal Tree Camptotheca acuminata

作者：Van‐Hung Bui, Joshua C. Wood, Brieanne Vaillancourt, John P. Hamilton, Lemor H. Carlton, Thu‐Thuy T. Dang, C. Robin Buell, Chenxin Li · 发表于：Plant Biotechnology Journal · 年份：2025 · DOI：10.1111/pbi.70386 · 被引用次数：3 · 研究领域：Cancer therapeutics and mechanisms、Protist diversity and phylogeny、Genomics and Phylogenetic Studies

Camptotheca acuminata Decne is a woody medicinal tree that produces over a hundred bioactive compounds, including camptothecin, which has been used as the starting material to semi-synthesise many leading anticancer drugs (Lorence and Nessler 2004). Camptothecin and its derivatives are potent inhibitors of DNA topoisomerase I and are widely used for the treatment of lung, cervical, ovarian and colon cancers. Camptothecin biosynthesis in C. acuminata involves complex catalytic steps, most of which remain undeciphered. In this pathway, tryptamine and secologanic acid are coupled, leading to strictosidinic acid. The formation of strictosidinic acid is catalysed by strictosidine/strictosidine acid synthase enzymes (STR) (Figure 1a). While a biosynthetic route for the conversion of the indole ring to the quinoline ring has been proposed, most of the underlying biosynthetic genes have yet to be identified (Figure 1a) (Sadre et al. 2016). In addition, the cell type specificity of this pathway also remains undescribed. Here, we generated a single cell multiome (RNA-seq and Assay for Transposase Accessible Chromatin by sequencing [ATAC-seq] from the same nuclei) to probe the cell type specificity of camptothecin biosynthetic genes. We performed organ-level metabolite profiling on key biosynthetic intermediates (Figure S1) across multiple C. acuminata organs and found that camptothecin was detected across all organs tested (Figure S1). Young leaf was chosen for single cell omics experi...