Division of Chemistry, Graduate School of Science , Hokkaido University , Sapporo 060-0810 , Japan.
Faculty of Agriculture , Tottori University , Tottori 680-8553 , Japan.
J Org Chem. 2018 Jul 6;83(13):7042-7048. doi: 10.1021/acs.joc.7b03220. Epub 2018 Feb 14.
The total biosynthesis of (-)-terpestacin was achieved by heterologous expression of four biosynthetic enzyme genes ( tpcA- D) in Aspergillus oryzae. After construction of preterpestacin I by the action of bifunctional terpene synthase (TpcA), two cytochrome P450s (TpcBC) activate inert C-H bond to install three hydroxyl groups on the A-ring in stereo- and regioselective manners. Subsequently, a flavin-dependent oxidase (TpcD) catalyzes oxidation of the vicinal diol moiety to give a α-diketone, which undergoes an enolization to furnish terpestacin. The successful synthesis of structurally elaborated terpestacin showed that a reconstitution approach that harnesses several biosynthetic enzyme genes in A. oryzae could be a promising alternative to the current chemical synthesis of natural terpenoids.
(-)-terpestacin 的全合成是通过在米曲霉中异源表达四个生物合成酶基因（tpcA-D）来实现的。在双功能萜烯合酶（TpcA）作用下构建前-terpestacin I 后，两个细胞色素 P450（TpcBC）以立体和区域选择性的方式激活惰性 C-H 键，在 A 环上安装三个羟基。随后，黄素依赖型氧化酶（TpcD）催化邻二醇部分的氧化生成α-二酮，该二酮经历烯醇化反应生成 terpestacin。结构复杂的 terpestacin 的成功合成表明，在米曲霉中利用多个生物合成酶基因的重建方法可能是替代当前天然萜类化合物化学合成的一种有前途的方法。
