Discovery and Engineering of Cytochrome P450s for Terpenoid Biosynthesis

Terpenoids represent 60% of known natural products, including many drugs and drug candidates, and their biosynthesis is attracting great interest. However, the unknown cytochrome P450s (CYPs) in terpenoid biosynthetic pathways make the heterologous production of related terpenoids impossible, while the slow kinetics of some known CYPs greatly limit the efficiency of terpenoid biosynthesis. Thus, there is a compelling need to discover and engineer CYPs for terpenoid biosynthesis to fully realize their great potential for industrial application. This review article summarizes the current state of CYP discovery and engineering in terpenoid biosynthesis, focusing on recent synthetic biology approaches toward prototyping CYPs in heterologous hosts. We also propose several strategies for further accelerating CYP discovery and engineering.