Toward Sustainable Paclitaxel Bioproduction: Plant Biology, Biosynthesis and Platform Engineering

Paclitaxel (Taxol), a taxane diterpenoid from Taxus species, is a clinically important microtubule-stabilizing anticancer agent widely used in chemotherapy. However, its supply remains limited by precursor scarcity and the molecule’s structural complexity. The biosynthetic pathway from geranylgeranyl diphosphate (GGPP) to paclitaxel is estimated to involve 19 to 23 enzymatic steps. Recent multi-omics approaches have substantially elucidated this pathway, yet key mechanistic questions persist, notably the formation of the oxetane ring. Complete heterologous biosynthesis is further hampered by poor cytochrome P450 (CYP) expression in non-native hosts and insufficient metabolic flux. This review synthesizes advances across four themes: (1) progressive elucidation of the biosynthetic pathway, with emphasis on the CYP-mediated oxygenation cascade and oxetane ring formation; (2) genomic and regulatory insights from Taxus genome assemblies, transcription factor networks, and spatial multi-omics; (3) metabolic engineering in microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, and non-conventional chassis; and (4) plant-based heterologous production platforms. Critical bottlenecks are identified, including unresolved enzymatic steps, CYP functional expression, flux partitioning, and bioprocess scale-up. Strategies to overcome these challenges are discussed.