Plant cytochrome P450s in triterpenoid biosynthesis: Diversity and application to combinatorial biosynthesis

Abstract

Plants produce a wide variety of specialized (secondary) metabolites, with which they interact in various environmental conditions for survival. Plant cytochrome P450s have a central function to enhance the diversity of the chemicals. Here we focus on the diversity of P450s in (tri)terpenoid biosynthesis and their application to combinatorial biosynthesis. A strategy combining a homology-based approach, gene coexpression analysis, and combinatorial biosynthesis with heterologous expression in yeast was successful in identifying enzymes involved in triterpenoid biosynthesis and also in generating natural and rare triterpenoids that do not accumulate in planta. Using this strategy is possible to construct a natural-unnatural triterpenoid library. The next steps are then to increase product yields as well as to diversify triterpenoids into novel synthetic entities with improved biological activities by combining enzymes from different sources.