TAILIEUCHUNG - Báo cáo khoa học: Manipulation of prenyl chain length determination mechanism of cis-prenyltransferases

The carbon backbones of Z,E-mixed isoprenoids are synthesized by sequentialcis-condensation of isopentenyl diphosphate (IPP) and an allylic diphosphate through actions of a series of enzymes calledcis-prenyltrans-ferases. Recent molecular analyses of Micrococcus luteusB-P 26 undecapre- | ềFEBS Journal Manipulation of prenyl chain length determination mechanism of cis-prenyltransferases Yugesh Kharel Seiji Takahashi Satoshi Yamashita and Tanetoshi Koyama Institute of Multidisciplinary Research for Advanced Materials Tohoku University Sendai Japan Keywords chain-length determination mechanism cisprenyltransferase isoprenoid biosynthesis Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase Correspondence T. Koyama Institute of Multidisciplinary Research for Advanced Materials Tohoku University Katahira 2-1-1 Aoba-ku Sendai 980-8577 Japan Fax 81 22 217 5620 Tel 81 22 217 5621 koyama@ Note Both authors contributed equally to this work. Received 28 October 2005 revised 9 December 2005 accepted 12 December 2005 doi The carbon backbones of Z E-mixed isoprenoids are synthesized by sequential ừs-condensation of isopentenyl diphosphate IPP and an allylic diphosphate through actions of a series of enzymes called cis-prenyltrans-ferases. Recent molecular analyses of Micrococcus luteus B-P 26 undecaprenyl diphosphate UPP C55 synthase Fujihashi M Zhang Y-W Higuchi Y Li X-Y Koyama T Miki K 2001 Proc Natl Acad Sci USA 98 4337-4342. showed that not only the primary structure but also the crystal structure of cis-prenyltransferases were totally different from those of trans-prenyltransferases. Although many studies on structure-function relationships of cis-prenyltransferases have been reported regulation mechanisms for the ultimate prenyl chain length have not yet been elucidated. We report here that the ultimate chain length of prenyl products can be controlled through structural manipulation of UPP synthase of M. luteus B-P 26 based on comparisons between structures of various cis-prenyl-transferases. Replacements of Ala72 Phe73 and Trp78 which are located in the proximity of the substrate binding site with Leu - as in Z E-farnesyl diphosphate C15 synthase - resulted in shorter ultimate products with

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