Stöckigt Joachim, Barleben Leif, Panjikar Santosh, Loris Elke A
College of Pharmaceutical Sciences, Zijingang Campus, Zhejiang University, 310058 Hangzhou, China.
Plant Physiol Biochem. 2008 Mar;46(3):340-55. doi: 10.1016/j.plaphy.2007.12.011. Epub 2008 Jan 3.
Strictosidine synthase (STR; EC 4.3.3.2) plays a key role in the biosynthesis of monoterpenoid indole alkaloids by catalyzing the Pictet-Spengler reaction between tryptamine and secologanin, leading exclusively to 3alpha-(S)-strictosidine. The structure of the native enzyme from the Indian medicinal plant Rauvolfia serpentina represents the first example of a six-bladed four-stranded beta-propeller fold from the plant kingdom. Moreover, the architecture of the enzyme-substrate and enzyme-product complexes reveals deep insight into the active centre and mechanism of the synthase highlighting the importance of Glu309 as the catalytic residue. The present review describes the 3D-structure and function of R. serpentina strictosidine synthase and provides a summary of the strictosidine synthase substrate specificity studies carried out in different organisms to date. Based on the enzyme-product complex, this paper goes on to describe a rational, structure-based redesign of the enzyme, which offers the opportunity to produce novel strictosidine derivatives which can be used to generate alkaloid libraries of the N-analogues heteroyohimbine type. Finally, alignment studies of functionally expressed strictosidine synthases are presented and the evolutionary aspects of sequence- and structure-related beta-propeller folds are discussed.
裂环马钱子苷合酶（STR；EC 4.3.3.2）通过催化色胺与裂环马钱子苷酸之间的Pictet-Spengler反应，在单萜吲哚生物碱的生物合成中起关键作用，专一性地生成3α-(S)-裂环马钱子苷。来自印度药用植物蛇根木的天然酶的结构代表了植物界六叶四链β-螺旋桨折叠的首个实例。此外，酶-底物和酶-产物复合物的结构深入揭示了合酶的活性中心和作用机制，突出了Glu309作为催化残基的重要性。本综述描述了蛇根木裂环马钱子苷合酶的三维结构和功能，并总结了迄今为止在不同生物体中进行的裂环马钱子苷合酶底物特异性研究。基于酶-产物复合物，本文接着描述了该酶基于结构的合理重新设计，这为生产新型裂环马钱子苷衍生物提供了机会，这些衍生物可用于生成N-类似物异育亨宾类型的生物碱文库。最后，展示了功能表达的裂环马钱子苷合酶的比对研究，并讨论了与序列和结构相关的β-螺旋桨折叠的进化方面。
