Changes in the Substrate Specificities of Farnesyl Diphosphate Synthase by a Single Amino Acid Substitution

二磷酸法尼酯（FPP）合成酶催化二磷酸异戊烯酯（IPP）与烯丙基引物缩合生成FPP。猪肝多糖已成功应用于生物活性化合物的合成。脂嗜热芽孢杆菌耐热性FPS基因的分子克隆和表达使生产足量的FPS酶成为可能。然而，它很难接受链上有氧原子的底物类似物，而猪肝酶很容易接受这些类似物。耐热酶在有机合成中的应用存在一定的局限性。我们从嗜热脂肪芽孢杆菌中构建了FPP合成（fps），其中tyr1 -81被Ser (S)、Arg (R)、Asp (D)或Gly (G)取代。有趣的是，突变酶的底物特异性已经显著改变。它们可以很容易地接受含有氧原子的底物类似物。这些结果可能表明戊烯基转移酶在有机合成中的应用是更可行的。

Farnesyl diphosphate (FPP) synthase catalyze the condensation of isopentenyl diphosphate (IPP) with allylic primer to give FPP as final product. The FPS from pig liver has been successfully applied to syntheses of bioactive compounds. Molecular cloning and expression of the gene for thermostable FPS from Bacillus stearothermophilus made it possible to produce sufficient amounts of the enzyme. However it can hardly accept the substrate analogs having oxygen atom in their chain, which are easily accepted by the pig the liver enzyme. There may be some limitations in the thermostable enzyme for applying to organic synthesis. We constructed the FPP syntheses (FPSs) from Bacillus stearothermophilus, in which Tyr-81 was substituted with Ser (S), Arg (R), Asp (D), or Gly (G). Interestingly the substrate specificities of the mutated enzymes have been dramatically altered. They can easily accept the substrate analogs having oxygen atom. These results may suggest the application of the prenyltransferases to organic synthesis is more available.