1. Jack Skirball Chemical Biology and Proteomics Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
2. Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Correspondence to: Stéphane B. Richard¹ Correspondence and requests for materials should be addressed to S.B.R (Email: richard@salk.edu).
The atomic coordinates and structure factors of Orf2 in complex with TAPS, Mg2 -GPP, Mg2 -GSPP-1,6-DHN and Mg2 -GSPP-flaviolin have been deposited in the Protein Data Bank under accession codes 1ZDY, 1ZCW, 1ZB6 and 1ZDW, respectively.

The anti-oxidant naphterpin is a natural product containing a polyketide-based aromatic core with an attached 10-carbon geranyl group derived from isoprenoid (terpene) metabolism^{1, 2, 3}. Hybrid natural products such as naphterpin that contain 5-carbon (dimethylallyl), 10-carbon (geranyl) or 15-carbon (farnesyl) isoprenoid chains possess biological activities distinct from their non-prenylated aromatic precursors⁴. These hybrid natural products represent new anti-microbial, anti-oxidant, anti-inflammatory, anti-viral and anti-cancer compounds. A small number of aromatic prenyltransferases (PTases) responsible for prenyl group attachment have only recently been isolated and characterized^{5, 6}. Here we report the gene identification, biochemical characterization and high-resolution X-ray crystal structures of an architecturally novel aromatic PTase, Orf2 from Streptomyces sp. strain CL190, with substrates and substrate analogues bound. In vivo, Orf2 attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during naphterpin biosynthesis. In vitro, Orf2 catalyses carbon–carbon-based and carbon–oxygen-based prenylation of a diverse collection of hydroxyl-containing aromatic acceptors of synthetic, microbial and plant origin. These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.