Sato Hajime, Uchiyama Masanobu, Saito Kazuki, Yamazaki Mami
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Cluster of Pioneering Research (CPR), Advanced Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Metabolites. 2018 Aug 31;8(3):48. doi: 10.3390/metabo8030048.
Lys-derived alkaloids widely distributed in plant kingdom have received considerable attention and have been intensively studied; however, little is known about their biosynthetic mechanisms. In terms of the skeleton formation, for example, of quinolizidine alkaloid biosynthesis, only the very first two steps have been identified and the later steps remain unknown. In addition, there is no available information on the number of enzymes and reactions required for their skeletal construction. The involvement of the Δ 1 -piperideine dimerization has been proposed for some of the Lys-derived alkaloid biosyntheses, but no enzymes for this dimerization reaction have been reported to date; moreover, it is not clear whether this dimerization reaction proceeds spontaneously or enzymatically. In this study, the energetic viability of the Δ 1 -piperideine dimerizations under neutral and acidic conditions was assessed using the density functional theory computations. In addition, a similar type of reaction in the dipiperidine indole alkaloid, nitramidine, biosynthesis was also investigated. Our findings will be useful to narrow down the candidate genes involved in the Lys-derived alkaloid biosynthesis.
广泛分布于植物界的赖氨酸衍生生物碱受到了广泛关注并得到了深入研究；然而，人们对其生物合成机制知之甚少。例如，就喹诺里西啶生物碱生物合成的骨架形成而言，仅确定了最初的两步，后续步骤仍不清楚。此外，关于其骨架构建所需的酶数量和反应，尚无可用信息。有人提出一些赖氨酸衍生生物碱的生物合成涉及Δ1-哌啶二聚化，但迄今为止尚未报道参与此二聚化反应的酶；此外，尚不清楚这种二聚化反应是自发进行还是由酶催化。在本研究中，使用密度泛函理论计算评估了中性和酸性条件下Δ1-哌啶二聚化的能量可行性。此外，还研究了二哌啶吲哚生物碱硝脒生物合成中的类似反应类型。我们的研究结果将有助于缩小参与赖氨酸衍生生物碱生物合成候选基因范围。
