亚洲喜树是喜树碱 (CPT) 的主要来源，因其卓越的抗肿瘤活性而受到越来越多关注。许多 CPT 衍生物在世界范围内作为有效的抗癌药物得到临床应用。然而，它们的生物合成机制仍不清楚，揭示这条路线将极大地促进开发替代 CPT 生产方法以取代目前低效的植物衍生方法。在十种亚洲喜树组织中，使用独特的分子识别符 RNA测序准确量化了> 30,000 基因的表达，并使用无标签定量蛋白质组学对来自五种组织的7,854个蛋白质进行了量化。使用长读取 Oxford Nanopore 技术对十五个全长转录本进行了测序，并在4,746个基因中发现了5,692个可变剪接事件。集成转录组和蛋白质组分析提供了有关 CPT 生物合成及其分层调节的新见解。五个细胞色素P450和三个O-甲基转移酶被认为是参与CPT及其衍生物的生物合成的候选者，而筛选出了十五个转录因子可能调节CPT生物合成。这些发现为阐明CPT及其衍生物的生物合成机制提供了重要线索，并实质性地有助于未来利用合成生物学生产这些抗癌药物。产生的大规模多组学数据也为研究最重要的CPT生产植物品种-亚洲喜树的功能基因组学提供了宝贵资源。本文受版权保护。版权所有。

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant-derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in ten C. acuminata tissues, and 7,854 proteins from five tissues were quantified with label-free quantitative proteomics. Fifteen full-length transcriptomes were sequenced with long-read Oxford Nanopore Technologies, and 5,692 alternative splicing events were discovered among 4,746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O-methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while fifteen transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large-scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT-producing plant species-C. acuminata. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.