Strictosidine synthase substrate specificities

Fig. 6 In vivo reprogramming of alkaloid biosynthesis in hairy roots of C. roseus by introduction of a mutant cDNA of the key enzyme strictosidine synthase (STR) with broader, unnatural substrate specificity leading to diversification of alkaloid content in roots following long-term feeding with 5-substituted tryptamines (X = Cl, Br, Me) [78]...

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). 

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... 

Substrate specificities of strictosidine synthase (STR) analogues from different sources, including heterologous expression, have been invest ted and reported. In summary, from about 30 tryptamine derivatives 10 were converted enzymatically to strictosidine analogues which could give rise to a variety of chemo-enzymatic approaches aiming to the construction of new alkaloids. The built-up alkaloid libraries based on strictosidine synthases was reviewed very recently. ... 

All monoterpenoid indole alkaloids are synthesized from strictosidine 44, which is a general biosynthetic intermediate formed by enzymatic condensation of trypt-amine with secologanin [162]. Recently, cDNA coding strictosidine synthase (E.C. 4.3.3.2) was isolated from 0. pumila and expressed further in E. coli. The enzyme has been characterized regarding its substrate specificity toward a number of tryptamines and activity regulation [163]. In another work distribution of strictosidine activity in O. pumila, tissues were shown to correlate with the pattern of respective mRNA expression [164]. 

McCoy, E. et al. (2006) Substrate specificity of strictosidine synthase. Bioorg. Med. Chem. Lett. 16,2475-2478... 

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