Unraveling the multispecificity and catalytic promiscuity of taxadiene monooxygenase

- This study is the first to report on multispecificity and catalytic promiscuity of taxadiene synthase and taxadiene 5α-hydroxylase, key enzymes in the paclitaxel biosynthetic pathway.
- The enzyme annotated as taxadiene 5α-hydroxylase acts on 4 substrates and forms 12 products. Taxadiene is converted by the enzyme to 5 products. In light of these results, it is proposed that taxadiene 5α-hydroxylase should be re-annotated as taxadiene monooxygenase.
- A reaction mechanism for the conversion of taxadiene to its 5 products is described in this report. This insight is based on results suggested by a novel computational methodology that was specifically developed to study the catalytic mechanism of the enzyme.