Core Viewpoint - The research team from East China University of Science and Technology has developed a non-natural oxidase toolbox for the selective oxidation of taxanes, which lays a solid foundation for the efficient synthesis of paclitaxel and its analogs [2][4]. Summary by Sections Research Development - The study published in Nature Communications focuses on designing an oxidase toolbox that enables site-directed oxidation at multiple positions (C-4, C-6, C-10, C-11, C-12, and C-13) of the taxane skeleton, resulting in the efficient synthesis of 11 new taxane structures [2][4]. - The research addresses the bottleneck in the biosynthesis of paclitaxel, which has been hindered by the low catalytic efficiency and poor expression of natural P450 enzymes responsible for multi-site oxidation [4][5]. Methodology - The team screened 29 types of fungal peroxidases and found that the non-specific peroxygenase TteUPO from Thielavia terrestris exhibited the highest oxidation activity towards taxadiene [4][5]. - The crystal structure of TteUPO was analyzed, leading to the redesign of the enzyme's substrate channel, which improved catalytic efficiency and expanded oxidation sites [5]. Outcomes - A toolbox containing seven key mutants was constructed, allowing for high regio- and stereoselective oxidation at six different sites on the taxane skeleton [5]. - This toolbox not only shows excellent catalytic performance for taxadiene but also for various higher oxidation state taxane derivatives, providing a rich set of enzymatic tools for the green biosynthesis of complex natural products like paclitaxel [5].