Structure and function of cis ‐prenyl chain elongating enzymes

All carbon skeletons of isoprenoids, whose chain lengths vary widely from geranyl diphosphate (C 10 ) to natural rubber (C >10,000 ), are synthesized by sequential condensation of isopentenyl diphosphate with an allylic diphosphate through catalytic functions of a group of enzymes commonly called “prenyltransferases.” Prenyltransferases are classified into two major groups, trans ‐ or ( E )‐prenyltransferases and cis ‐ or ( Z )‐prenyltransferases, according to the geometry of the prenyl chain units in the products. From the year 1987, many genes encoding trans ‐prenyltransferases were cloned and clearly characterized. In contrast, the structure and detailed mechanism of cis ‐prenyltransferase was completely unknown until the identification of a gene encoding the undecaprenyl diphosphate (UPP) synthase from Micrococcus luteus B‐P 26 in 1998. Not only the primary but also the tertiary structure of the UPP synthase is quite different from that of the trans ‐prenyltransferases. Multiple alignment of the primary structures of cis ‐prenyltransferases identified from various organisms reveals five highly conserved regions. Site‐directed mutagenesis of the conserved amino acid residues in UPP synthases based on the crystal structure has elucidated the basic catalytic mechanisms. Moreover, comparison of the structures of short‐, medium‐, and long‐chain cis ‐prenyltransferases reveals important amino acid residues for product chain length determination, which enabled us to understand the regulation mechanism of the ultimate chain length among cis ‐prenyltransferases. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 194–205; 2006: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20083