3D-Structure and function of strictosidine synthase - the key enzyme of monoterpenoid indole alkaloid biosynthesis

作者：Stoeckigt Joachim; Barleben Leif; Panjikar Santosh; Loris Elke A^*

来源：Plant Physiology and Biochemistry, 2008, 46(3): 340-355.

DOI：10.1016/j.plaphy.2007.12.011

• strictosidine synthase
• Biological Pictet-Spengler reaction
• 3D-structure
• beta-propeller fold architecture of substrates and product complexes
• enzyme mechanism
• rational redesign
• monoterpenoid indole alkaloids
• biosynthesis
• Rauvolfia serpentina

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 3 alpha-(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 P-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 P-propeller folds are discussed.

• 出版日期2008-3
• 单位浙江大学