Strictosidine synthase structures

The power of engineered enzymes in the synthesis of novel alkaloids, to generate structural diversity and establish new alkaloid libraries, is best represented by the enzyme strictosidine synthase (STR1). 

All terpenoid indole alkaloids are derived from tryptophan and the iridoid terpene secologanin (Fig. 2b). Tryptophan decarboxylase, a pyridoxal-dependent enzyme, converts tryptophan to tryptamine (62, 63). The enzyme strictosidine synthase catalyzes a stereoselective Pictet-Spengler condensation between tryptamine and secologanin to yield strictosidine. Strictosidine synthase (64) has been cloned from the plants C. roseus (65), Rauwolfla serpentine (66), and, recently, Ophiorrhiza pumila (67). A crystal structure of strictosidine synthase from R. serpentina has been reported (68, 69), and the substrate specificity of the enzyme can be modulated (70). 

Ma X, Panjikar S, Koepke J, Loris E, Stockigt J. The structure of 86. Rauvolfia serpentina strictosidine synthase is a novel six-bladed beta-propeller fold in plant proteins. Plant Cell 2006 18 907-920. 

The basic structure of monoterpenoid indole alkaloids includes an indole nucleus derived from tryptophan via tryptamine (L) and a versatile C9 or CIO unit arising from the monoterpenoid secologanin (LI). Strictosidine synthase catalyzes the synthesis of strictosidine (LII) from tryptamine and secologanin (Scheme XXIV) [76],... 

A key step in indole alkaloid biosynthesis is the formation of strictosidine from tryptamine and the aldehyde secologanin [357, 358]. This reactimi is catalyzed by the enzyme strictosidine synthase. The crystal structure of the enzyme has been determined and the binding site identified [359]. Site-directed mutagenesis has been used to identify both the active site amino acids and to modify the substrate specificity of the enzyme [360]. The enzymatic mechanism has been compared with the H -catalyzed reaction in solution and they appear to be similar, based on... 

The enzyme family of strictosidine synthases is stiU very small and only one member, STRl from Rauvolfia has been structurally well defined. Because of the chemoenzymatic significance, this family should be investigated in more detail. However, it seems that similar enzymes members... 

Stockigt, J., et al., 3D-Structure and function of strictosidine synthase—the key enzyme of monoterpenoid indole alkaloid biosynthesis. Plant Physiol Biochem., 2008. 46(3) p. 340-55. 

Loris EA et al (2007) Structure-based engineering of strictosidine synthase auxiliary for alkaloid libraries. Chem Biol 14 979-985... 

---