Blaine A. Pfeifer, Chemical and Biological Engineering, Tufts University, 4 Colby Street, Medford, MA 02155
The potent anticancer agent Taxol is a plant-derived terpenoid natural product. Current production schemes depend upon plant- or plant cell culture-driven processes and, as such, are potentially limited in maximum productivities and the ability to genetically engineer the biosynthetic process. In this presentation, initial results will be presented for the production of early stage Taxol intermediates from the heterologous host E. coli. Metabolic engineering was required for both native and foreign gene manipulation. First, native E. coli metabolism was altered to provide boosted levels of intracellular precursors capable of supporting terpenoid biosynthesis. Next, the fist dedicated steps of Taxol biosynthesis were introduced to E. coli using tools of both heterologous metabolic engineering and synthetic biology. Upon confirming reconstituted biosynthesis, more recent efforts have focused on pathway and process metabolic engineering for the improvement of heterologous product yields.
