Institute of Materia Medica, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
J Am Chem Soc. 2012 Jan 25;134(3):1498-500. doi: 10.1021/ja211524d. Epub 2012 Jan 9.
The Pictet-Spenglerase strictosidine synthase (STR1) has been recognized as a key enzyme in the biosynthesis of some 2000 indole alkaloids in plants, some with high therapeutic value. In this study, a novel function of STR1 has been detected which allows for the first time a simple enzymatic synthesis of the strictosidine analogue 3 harboring the piperazino[1,2-a]indole (PI) scaffold and to switch from the common tryptoline (hydrogenated carboline) to the rare PI skeleton. Insight into the reaction is provided by X-ray crystal analysis and modeling of STR1 ligand complexes. STR1 presently provides exclusively access to 3 and can act as a source to generate by chemoenzymatic approaches libraries of this novel class of alkaloids which may have new biological activities. Synthetic or natural monoterpenoid alkaloids with the PI core have not been reported before.
Pictet-Spenglerase 严格吲哚乙胺合酶（STR1）已被认为是植物中约 2000 种吲哚生物碱生物合成的关键酶，其中一些具有很高的治疗价值。在这项研究中，检测到 STR1 的一个新功能，这使得首次能够通过简单的酶促合成含有哌嗪并[1,2-a]吲哚（PI）支架的严格吲哚类似物 3，并从常见的色胺啉（氢化咔啉）转换为罕见的 PI 骨架。通过 STR1 配体复合物的 X 射线晶体分析和建模提供了对反应的深入了解。STR1 目前仅提供对 3 的访问途径，并可以作为通过化学酶法途径生成该新型生物碱类文库的来源，这些文库可能具有新的生物活性。以前没有报道过具有 PI 核心的合成或天然单萜生物碱。
