Galaxon Researchers Discovered Novel Gene in Making New Cancer Drug

The new enzyme, which was first cloned and discovered from the English yew tree Taxus baccata by Galaxon researchers, is involved in the final step of conversion from paclitaxel to a related compound, which the researchers named as "novataxel". The enzyme was named as 3’-N-benzyl-2’-deoxytaxol-N-benzoyltransferase (BTNBT), and is functionally similar to 3’-N-debenzoyl-2’-deoxytaxol-N-benzoyltransferase (DBTNBT), which is involved in the addition of benzoyl group to the chemical compound. 

There are a total of 13 enzymes involved in the biosynthesis of novataxel from the glucose precursor, and this complex metabolic pathway can be divided into three distinct phases, with different intermediates and enzymes involved. Novataxel biosynthesis begins from glucose with Phase I leading to the production of isopentenyldiphosphate (IPP) and dimethylallyldiphosphate (DMAPP), which are actually isoprene precursors originated from the plastidial methyl-erythritol phosphate (MEP) pathway (Vongpaseuth, 2011) . These two precursors would then be directed to the second phase of the pathway, in which a taxadiene – an important precursor of novataxel – is generated. Finally, in Phase III, several acylation steps, along with side chain generation, conjugation and modification are involved in the biosynthesis of the final product – novataxel.