A study has elucidated the biosynthetic pathway of Taxol, a widely used anticancer drug, focusing on the formation of its highly oxygenated tetracyclic core skeleton. The research identified key enzymes and reaction steps, including the critical hydroxylation steps and the role of CYP725A55 in oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. The study confirmed the biosynthesis of 1β-dehydroxybaccatin VI, a highly oxygenated Taxol intermediate, from taxa-4(20),11(12)-diene-5α-ol in engineered yeast. The pathway involves multiple enzymatic steps, including hydroxylation, acetylation, and oxidation reactions, and highlights the importance of acetyltransferases and P450 enzymes in the biosynthesis. The study also revealed the formation of the Taxol tetracyclic core skeleton through a complex process involving acyl rearrangement and oxidation. The findings provide a foundation for further elucidation of the complete Taxol biosynthetic pathway and have implications for the development of synthetic methods and biotechnological applications. The research underscores the complexity of Taxol biosynthesis and the importance of understanding the enzymatic mechanisms involved in its production.A study has elucidated the biosynthetic pathway of Taxol, a widely used anticancer drug, focusing on the formation of its highly oxygenated tetracyclic core skeleton. The research identified key enzymes and reaction steps, including the critical hydroxylation steps and the role of CYP725A55 in oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. The study confirmed the biosynthesis of 1β-dehydroxybaccatin VI, a highly oxygenated Taxol intermediate, from taxa-4(20),11(12)-diene-5α-ol in engineered yeast. The pathway involves multiple enzymatic steps, including hydroxylation, acetylation, and oxidation reactions, and highlights the importance of acetyltransferases and P450 enzymes in the biosynthesis. The study also revealed the formation of the Taxol tetracyclic core skeleton through a complex process involving acyl rearrangement and oxidation. The findings provide a foundation for further elucidation of the complete Taxol biosynthetic pathway and have implications for the development of synthetic methods and biotechnological applications. The research underscores the complexity of Taxol biosynthesis and the importance of understanding the enzymatic mechanisms involved in its production.