3. **Mechanistic Insights Using Isotope Labeling and DFT Calculations**: Mechanistic studies, including **deuterium and oxygen-18 (18O) labeling**, were performed to understand how the oxetane ring forms. The results revealed that the formation likely occurs through an **intramolecular oxidation-acetoxyl rearrangement**, with migration of the acetoxy group from C5 to C4. The authors proposed a mechanism in which the oxetane ring is formed via a concerted process, rather than through stepwise processes previously hypothesized. . **Probing of the Enzymatic Pathway with a Broader Substrate Scope**: The paper expanded on the enzyme's substrate scope by synthesizing a series of taxadienes with varying oxygenation levels and testing their conversion by TmCYP1. The enzyme was found to selectively catalyze oxetane formation in substrates that were highly oxygenated, reinforcing the hypothesis that oxetane ring formation occurs at a late stage in paclitaxel biosynthesis when the taxadiene structure is highly substituted with oxygen functional groups.