Aug 2026· The Plant Genome· Vol 19· 0 citations· 104 references
Medicine
TL;DR
This study engineered an experimental callus system for inducible production of CPT, which enabled multi‐omics and deep learning analyses to identify candidate genes in CPT biosynthesis and provides a valuable foundation for the complete elucidation of the CPT biosynthetic pathway.
Abstract
Abstract Camptothecin (CPT), a plant‐derived monoterpene indole alkaloid first identified in Camptotheca acuminata, is a drug precursor widely used for cancer chemotherapeutics. However, the full set of genes responsible for CPT biosynthesis remains unclear, hindering efforts to elucidate the complete pathway or establish biosynthetic production of CPT in heterologous hosts. In this study, we engineered an experimental callus system for inducible production of CPT, which enabled multi‐omics and deep learning analyses to identify candidate genes in CPT biosynthesis. We first generated an improved genome assembly and gene annotation for C. acuminata. We then leveraged the natural variation of CPT levels in C. acuminata tissues and performed transcriptomic analysis of multiple callus and tissue types to shortlist candidate enzymes responsible for CPT biosynthesis. Finally, we conducted large‐scale deep learning–enabled protein–ligand complex structure prediction to prioritize 117 candidate enzymes for studies that map their roles in CPT biochemical reactions. By integrating experimental, genomic, transcriptomic, and deep learning approaches, this study provides a valuable foundation for the complete elucidation of the CPT biosynthetic pathway.
Findings reveal tissue-specific metabolite accumulation and key genes involved in MIA biosynthesis in N. cadamba that provide valuable insights into specialized metabolism and establish a foundation for future metabolic engineering and functional genomics studies.
Divya Selvakumar, G. Ramalingam, Suganya Balan et al.· Molecular Biology Reports· 0 citations
Taxol (paclitaxel) is a frontline anticancer drug widely applied for the treatment of breast, ovarian and lung cancers. Currently, its supply mainly relies on the semi-synthesis using baccatin III from Taxus plants. Heterologous biosynthesis of baccatin III in microorganisms offers a promising solution to alleviate global Taxol supply shortage, but remains challenging due to pathway complexity. Here, we report a novel taxusin-mediated biosynthetic pathway for baccatin III production via the identification of C13 deacetylase, elucidation of the exact sequence underlying C1 hydroxylation, and stepwise enzymatic functional validation. Through protein engineering of the promiscuous C1 and C5 hydroxylases, coupled with the distribution of pathway modules in Saccharomyces cerevisiae and Escherichia coli, we achieved the de novo biosynthesis of baccatin III. Collectively, our findings remodel the current biosynthetic framework governing the formation of Taxol precursors and highlight the great potential of microbial cell factories for the production of complex plant-derived therapeutic compounds. Highlights • Discovery of C13 deacetylase reveals a novel biosynthetic route to baccatin III via taxusin • Stepwise verification of the complete biosynthetic route to baccatin III through taxusin and baccatin VI • Single-site mutation reversed the product selectivity of T1OH and converted T5OH into a specific taxoid C5 hydroxylase • Complete biosynthesis of baccatin III in engineered microbes
The biosynthetic potency of CPT and their molecular regulatory processes to sustain the CPT productivity by fungi are unraveled by exploring the rate-limiting enzymes, epigenetic regulators and transcriptional factors of CPT biosynthesis.
Ashraf S. A. El-Sayed, Marwa A. Yassin, Ashraf Farag El‐Baz· Discover Applied Sciences· 0 citations
This review compares the historical and methodological trajectories that have shaped IA and AA pathway elucidation, from compound isolation, radiotracer experiments, and biochemical inference to transcriptomics, metabolomics, functional enzymology, isotope-guided active-tissue identification, regulatory studies, and heterologous pathway reconstruction.
Mateo Peña-Morales, J. D. Vega-Páez, Natalie Cortes et al.· Plants· 0 citations
Findings provide insights into the potential multifaceted insecticidal action of benzothiazole in T. castaneum at the transcriptomic level and support its further development as a target-specific grain fumigant.
Kaidi Cui, Xueran Hu, Weifeng Cheng et al.· Pest Management Science· 0 citations