<jats:title>Significance</jats:title> <jats:p> Metabolic engineering is an economically feasible and sustainable alternative for the production of natural products, pharmaceuticals, nutraceuticals, flavors, and fragrances. Of the model systems used to demonstrate and develop this approach, the anticancer agent Taxol stands out for its structural complexity and therapeutic value. A major challenge for the biosynthesis of Taxol and many other natural products is the involvement of cytochrome P450-mediated oxygenation. P450 enzymes are intransigent to functional heterologous expression, especially in <jats:italic>Escherichia coli</jats:italic> , leading many laboratories to abandon this organism when engineering P450-containing pathways. Here, through a series of optimizations, we demonstrate <jats:italic>E. coli</jats:italic> as a viable host for P450-mediated oxidative chemistry, advancing Taxol’s biosynthesis through a fivefold increase in oxygenated terpene titers.