Novel Aromatic Prenyltransferases, Nucleic Acids Encoding Same and Uses Therefor

Inventors: Joseph P. Noel, Stephane Richard, Tomohisa Kuzuyama
Potential Uses: Drug Discovery and Development
Enzyme that transfers a prenyl group is found to be unexpectedly promiscuous

A bacterial enzyme that transfers a prenyl group to an aromatic natural product may provide a general biosynthetic route to regioselective prenylation of aromatic small molecules.

Many bioactive natural products contain isoprenoid chains of various lengths, collectively known as prenyl groups. New research has revealed biochemical and structural characterization of Orf2, a prenyltransferase enzyme that attaches a 10-carbon prenyl group to a polyketide during the biosynthesis of the antioxidant naphterpin. This enzyme has a novel barrellike architecture and is unexpectedly promiscuous. In vitro, Orf2 can regiospecifically prenylate a diverse collection of hydroxyl-containing aromatic molecules of microbial, plant, and synthetic origin.

New information on the factors that control which prenyl chain is used and where it's appended on the substrate should guide the design of modified enzymes that can be used to alter the activity of natural products in bacteria, fungi, plants, and animals. This makes it possible to make rare prenylated natural products; and to carry out regioselective prenylation of aromatic chemicals.