Structural basis of cycloaddition in biosynthesis of iboga and aspidosperma alkaloids

被引:0
作者
Lorenzo Caputi
Jakob Franke
Kate Bussey
Scott C. Farrow
Ivo Jose Curcino Vieira
Clare E. M. Stevenson
David M. Lawson
Sarah E. O’Connor
机构
[1] Max Planck Institute of Chemical Ecology,
[2] Department of Natural Product Biosynthesis,undefined
[3] Leibniz University Hannover,undefined
[4] Centre for Biomolecular Drug Research,undefined
[5] John Innes Centre,undefined
[6] Department of Biological Chemistry,undefined
[7] Norwich Research Park,undefined
[8] Laboratorio de Ciencias Quimicas-UENF-Campos dos Goytacazes-RJ,undefined
来源
Nature Chemical Biology | 2020年 / 16卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Cycloaddition reactions generate chemical complexity in a single step. Here we report the crystal structures of three homologous plant-derived cyclases involved in the biosynthesis of iboga and aspidosperma alkaloids. These enzymes act on the same substrate, named angryline, to generate three distinct scaffolds. Mutational analysis reveals how these highly similar enzymes control regio- and stereo-selectivity.
引用
收藏
页码:383 / 386
页数:3
相关论文
共 63 条
[1]  
O’Connor SE(2006)Chemistry and biology of monoterpene indole alkaloid biosynthesis Nat. Prod. Rep. 23 532-472
[2]  
Maresh JJ(2018)Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle Science 60 1235-1239
[3]  
Caputi L(1962)Biosynthesis of indole alkaloids. The aspidosperma and iboga bases J. Am. Chem. Soc. 84 98-102
[4]  
Wenkert E(1969)Mechanisms of indole alkaloid biosynthesis. The Corynanthe-Strychnos relationship J. Am. Chem. Soc. 91 4932-4936
[5]  
Scott AI(1968)Studies on indole alkaloid biosynthesis. II J. Am. Chem. Soc. 90 5929-5930
[6]  
Cherry PC(2019)Biosynthesis of an anti-addiction agent from the iboga plant JACS 141 12979-12983
[7]  
Qureshi AA(1970)Biosynthesis of the indole alkaloids Acc. Chem. Res. 3 151-157
[8]  
Kutney JP(1968)Biogenetic-type synthesis of Iboga alkaloids: (±)-catharanthine J. Chem. Soc. Chem. Commun. 16 947-948
[9]  
Ehret C(1978)Studies in biomimetic alkaloid syntheses. 2. Synthesis of vincadifformine from tetrahydro-beta-carboline through a secodine intermediate Org. Chem. 43 3705-3710
[10]  
Nelson VR(2003)The carboxylesterase gene family from J. Mol. Evol. 57 487-500