Sesquiterpenoids Produced by the Combination of Two Sesquiterpene Cyclases with Promiscuous Myxobacterial CYP260B1.

Sesquiterpenes represent a class of important terpenoids with high structural diversity and a wide range of applications. The cyclized core-skeletons are generated by sesquiterpene cyclases, and the structural diversity is further increased by a series of modification steps. Cytochromes P450 (P450s) are a class of monooxygenases and one of the main contributors for the structure diversity of natural products. Some of these P450s show a broad substrate range and might be promising candidates for the implementation of cascade reactions. In this study, a combinatorial biosynthesis strategy was utilized by the combination of a promiscuous myxobacterial P450 (CYP260B1) with two sesquiterpene cyclases (FgJ01056, FgJ09920) of filamentous fungi. Two oxygenated products, culmorin, culmorone, and a new compound, koraidiol, were successfully generated and characterized. This approach suggests the potential use of non-cognate P450s to produce novel oxygenated terpenoids, or to generate a novel biosynthetic route for known terpenoids by a combinatorial biosynthesis strategy.