br Acknowledgments br Introduction Prenyltransferase catalyz

Acknowledgments
Introduction Prenyltransferase catalyzes the head-to-tail condensation between isopentenyl diphosphate (IPP, 1) and an allylic prenyl diphosphate to produce several prenyl diphosphates, which are then converted into steroids, carotenoids, prenyl side-chains of quinones, and prenyl proteins (Scheme 1) [1], [2], [3], [4]. Among prenyltransferases, farnesyl diphosphate (FPP) synthase [EC 2.5.1.10] plays an important role in early stage metabolic reactions in isoprenoid chemistry. FPP synthase exists almost universally in higher animals and bacteria, except for archaebacteria, and catalyzes the condensation of IPP and dimethylallyl diphosphate (2) via geranyl diphosphate (3) to farnesyl diphosphate (FPP, 4) (Scheme 2). Several studies have investigated the substrate specificities of FPP synthase with allylic and homoallylic substrate homologs [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. For example, Koyama et al. reported that synthesis of chiral molecules by an enzymatic reaction is a useful method of building biologically active substances such as trail marker pheromones or juvenile ibuprofen solubility [15], [16], [17], [18], [19], [20]. Our previous research on substrate specificity involving homoallylic substrate homologs such as 4-alkyl (methyl, ethyl, propyl, or butyl) group homologs of IPP indicated that FPP synthase is useful in the synthesis of chiral compounds. Farnesol homologs with an alkyl group at the 4-position with (S)- or (R)-configuration can be selectively prepared from (E)- or (Z)-4-alkylIPP, respectively [21]. Among the studies investigating cyclic substrate homologs using FPP synthase, Koyama et al. reported on the substrate specificity of FPP synthase with respect to cyclic compounds [12]. In order to get advanced insight into some artificial substrate homologs having cyclic structures, we will describe here some different properties of the substrate specificities between two FPP synthases from Bacillus stearothermophilus and from porcine liver.
Experimental
Results and discussion To investigate the reactivities of cyclic allyl and homoallyl substrate homologs, we examined substrate specificities of FPP synthases derived from B. stearothermophilus and porcine liver.
Conclusion To investigate substrate specificities of FPP synthases derived from B. stearothermophilus and porcine liver, we examined the reactivities of cyclic substrate homologs 5 and 7. Reaction of 3 with 5 produced (S)-6 with relative reactivities of 13.6% for bacterial and 42.2% for porcine liver synthase. In contrast, reaction of 7 with 1 using bacterial FPP synthase gave a double-condensation product, 9 (yield: 23.1%), as the main product, with only a trace of 8. Reaction of 7 with 5 using bacterial FPP synthase produced 10 (0.8% yield) exclusively. In conclusion, both 5 and 7 were found to be acceptable substrates for FPP synthases. These findings are interesting with regard to models of chiral synthesis in organic chemistry, and may aid future researchers in successfully synthesizing biologically active chiral substances.
Acknowledgments
Introduction Farnesyl pyrophosphate synthase (FPPS) can be considered as a valid target not only for bone related disorders, but also for different parasitic diseases. FPPS catalyzes the consecutive condensation of IPP with DMAPP and with geranyl diphosphate (GPP) to produce farnesyl diphosphate (FPP). FPP is the substrate for enzymes catalyzing the first committed step for the biosynthesis of sterols, ubiquinones, dolichols, heme a, and prenylated proteins. FPP could be condensed with an additional molecule of IPP by the geranylgeranyl pyrophosphate synthase (GGPPS) to form the 20-carbon isoprenoid GGPP. In trypanosomatids, isoprenoid biosynthesis occurs via the classical mevalonate pathway (Scheme 1). The FPPS gene has been cloned from Trypanosoma cruzi and Trypanosoma brucei.2, 3 Both of these genes are single copy. RNA interference showed that the T. brucei FPPS gene is essential.