A minimal transcription factor network is sufficient to drive paclitaxel biosynthesis

The supply of the anticancer drug paclitaxel is limited by its low natural abundance and complex chemical structure. We previously reported the development of a cultured Taxus cambial meristematic cell (CMC) system, where methyl jasmonate enhances paclitaxel production. In this report, we describe a comprehensive analysis to identify potential master regulators of paclitaxel biosynthesis. We report that the combined expression of two myeloblastosis transcription factors can cooperatively activate a subset of paclitaxel biosynthetic genes in stable transgenic CMCs, resulting in a 121-fold increase in paclitaxel and a 364-fold increase in its valuable precursor baccatin III. Our findings provide a powerful approach to enhancing production of this vital compound and can also be applied to other valuable products.