Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli

Abstract

Toward Microbial Taxol Taxol, a minor chemical constituent of yew tree bark, has provided a potent cancer treatment. Production methods presently rely on plant cell cultures. Ajikumar et al. (p. 70 ; see the Perspective by Liu and Khosla ) engineered Escherichia coli cells to produce a key taxol precursor, in which the polycyclic carbon skeleton is intact. The approach relied on optimizing the relative activity of two pathways, the first of which synthesized isoprenoid building blocks that were then stitched together with the second pathway. Accumulation of indole as a by-product inhibited the isoprenoid pathway—an insight that should facilitate more efficient engineered biosynthesis of a wide range of commercially important isoprenoid derivatives.