Intermolecular Carbon–Carbon Bond Formation by a Chorismate-Converting Enzyme

Abstract Chorismate is an important precursor of many primary and secondary metabolites. Enzymes that can transform chorismate are therefore useful biocatalysts for constructing bioactive molecules, yet the scope of known chorismate biochemistry is limited. Here, we identify TunB, an enzyme that catalyzes an intermolecular carbon–carbon bond formation with chorismate in the absence of any cofactors. TunB is involved in the biosynthesis of tundrenone, a natural product produced by a methane-oxidizing bacterium, and was not predicted to use chorismate as a substrate on the basis of amino acid sequence homology. The discovery of the function of TunB therefore reveals an unexpected chorismate-converting enzyme that may enable the construction of additional scaffolds based on this important metabolite.