Systematic prioritization of candidate genes in camptothecin biosynthesis using multi‐omics and deep learning

Metabolomic and transcriptomic analyses reveal the monoterpenoid indole alkaloid biosynthesis in Neolamarckia cadamba

Discovery of a taxusin-mediated route to baccatin III enables its complete biosynthesis in engineered microbes

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

Biosynthesis and molecular regulatory mechanisms of camptothecin in fungi

Camptothecin (CPT) is one of the common chemotherapies for tumors, for its superior affinity for inhibiting the Topoisomerase I activity via stabilizing the enzyme–DNA ternary complex, thus precluding the relaxation of DNA in the frequently replicated cells. CPT was initially derived from the bark of chinese Happy tree plants “Camptotheca acuminata”. However, availability of the CPT and their derivatives is the main challenge that halts the further implementation of this compound. The fungal biosynthetic potency of CPT raises the prospective for the production of CPT, due to their short lifespan and feasibility of bulk biomass bioprocessing, nevertheless, weakening of the CPT productivity with the fungal storage consecutive subculturing are the challenge. So, this review was to unravel the biosynthetic potency of CPT and their molecular regulatory processes to sustain the CPT productivity by fungi by exploring the rate-limiting enzymes, epigenetic regulators and transcriptional factors of CPT biosynthesis. As well as, to explore the expression of CPT biosynthetic gene clusters regarding to chromatin remodeling, microbial-microbial crosstalk, in relation to deciphering the CPT biosynthesis gene cluster by fungi.

Transcriptomic landscape of Cestrum diurnum: elucidating pathways of medicinally important terpenoids and toxic alkaloids

Amaryllidaceae Alkaloids and Isoquinoline Alkaloids: A Perspective on Historical Approaches to Pathway Elucidation

Alkaloid biosynthesis is a central topic in plant specialized metabolism because many alkaloids have ecological, pharmacological, and biotechnological relevance. Isoquinoline alkaloids (IAs) and Amaryllidaceae alkaloids (AAs) are both connected to aromatic amino acid metabolism, but they differ in taxonomic distribution, scaffold-forming chemistry, pathway resolution, and biotechnological development. 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. In IAs, especially benzylisoquinoline alkaloids, broad genomic and transcriptomic resources have supported candidate gene discovery and functional characterization of several branches, including morphinan, protoberberine, benzophenanthridine, and aporphine-related pathways. In contrast, AA biosynthesis has advanced more recently through function-driven approaches that clarified key steps such as N4OMT-mediated 4′-O-methylation, NBS/NR-mediated norbelladine formation, CYP96T-dependent regioselective oxidative coupling, and transient reconstruction of major scaffold-forming branches. Remaining gaps include the unresolved enzymatic formation of 3,4-dihydroxybenzaldehyde in AAs and incomplete functional validation across less-studied IA scaffold classes. By integrating biochemical logic, omics-guided discovery, enzyme evolution, tissue specificity, regulation, and synthetic biology, this review identifies priorities for future alkaloid pathway discovery and sustainable production.

Molecular response of Tribolium castaneum to benzothiazole: insights from transcriptome and functional validation of UGT2B9.

BACKGROUND Benzothiazole has been identified as a potential grain fumigant against Tribolium castaneum, though its insecticidal mechanism requires further investigation. In this study, sixth-instar larvae of T. castaneum were exposed to benzothiazole at LC30 and LC50 concentrations for 24 h. RESULTS Neither concentration caused sustained inhibition of larval respiratory rate, ATP content, or mitochondrial membrane potential over the 24 h exposure period. RNA-seq analysis identified 392 differentially expressed genes common to both LC30 (50.96 μL L-1) and LC50 (108.86 μL L-1) treatments. Protein-protein interaction analysis of these shared genes revealed three core genes all encoding 4-coumarate-CoA ligase (4CL). In larvae, benzothiazole exposure upregulated genes in pathways related to protein digestion and absorption, juvenile hormone hydrolysis, detoxification and cuticle formation, but downregulated genes in carbohydrate metabolism. Among the key genes involved, UDP-glucuronosyltransferases (UGTs) participated in multiple enriched pathways and emerged as a common responsive gene family in both T. castaneum and the Dipteran insect Bradysia odoriphaga. RNAi-mediated silencing of UGT2B9, 4CL, or extensin demonstrated that only knockdown of UGT2B9 significantly increased larval susceptibility to benzothiazole. CONCLUSION These 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. © 2026 Society of Chemical Industry.