Strictosidine glucosidase, biosynthesis

Fig. 8.1 Sequence of reactions and pathways involved in the biosynthesis of indole alkaloids in Catharanthus roseus. The dotted lines indicate multiple and/or uncharacterized enzyme steps. Tryptophan decarboxylase (TDC), Geraniol Hydroxylase (GH), Deoxyloganin synthase (DS), Secologanin Synthase (SLS) Strictosidine synthase (STR1), Strictosidine glucosidase (SG), Tabersonine-16-hydroxylase (T16H), Tabersonine 6,7-eposidase (T6,7E), Desacetoxyvindoline-4-hydroxylase (D4H), Deacetyl-vindoline-4-O-acetyltransferase (DAT) and Minovincinine-19-O-acetyltransferase (MAT) represent some of the enzyme steps that have been characterized.

T. J. C. Luijendijk, Strictosidine glucosidase in alkaloid biosynthesis. Ph.D. Thesis, Leiden University, 1995. 

Figure Simplified scheme for the biosynthesis of the antiar- > rhythmic agent ajmaline. Only the key steps are shown in the scheme. The cofactors given on the left side participate in individual enzymatic reactions. The following enzymes were identified in the 15-step sequence leading to the final product ajmaline 1 strictosidine synthase 2 strictosidine glucosidase ...

Fig. 8.5 Compartmentation of alkaloid biosynthesis in Cathamnthus roseus. AS anthianilate synthase, CR NADPH cathenamine reductase, DAT deacetylvindoline 17-O-acetyltransferase, ER endoplasmic reticulum, GlOH geraniol 10-hydroxylase, GAP glyceraldehyde-3-phosphate, NMT S-adenosyl-L-methionine methoxy-2, 16-dihydro-16-hydioxylagersonine-lV-methyltransferase, OHT desacetoxyvindoline-4-hydroxylase, SGD strictosidine -glucosidase, STR strictosidine synthase TDC tryptophan decarboxylase, THAS NADPH tetrahydroalstonine reductase (Adopted from Ref. [10])... 

Barleben, L. et al. (2007) Molecular architecture of strictosidine glucosidase the gateway to the biosynthesis of the monoterpenoid indole alkaloid family. Plant Cell 19,2886-2897... 

Fig. 3. Biosynthesis of TIAs in C. roseus. Solid arrows indicate single enzymatic conversions, whereas dashed arrows indicate multiple enzymatic conversions. AS Anthranilate synthase, DXS D-l-deoxyxylulose 5-phosphate synthase G10H geraniol 10-hydroxylase CPR cytochrome P450 reductase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine /1-D-glucosidase D4H desacetoxyvindoline 4-hydroxylase DAT acetyl-CoA 4-O-deacetylvindoline 4-O-acetyl transferase. Genes regulated by ORCA3 are underlined. Reprinted with permission from [91]. Copyright (2000) American Association for the Advancement of Science...

GEERLINGS, A., MARTINEZ-LOZANO IBANEZ, M., MEMELINK, J., VAN DER HEIJDEN, R., VERPOORT, R., Molecular cloning and analysis of strictosidine P-D-glucosidase, an enzyme in terpenoid indole alkaloid biosynthesis in Catharanthus roseus. J. Biol. Chem., 2000,275,3051-3056. 

The versatility of strictosidine as a central intermediate for the biosynthesis of a variety of alkaloids is based on the highly reactive dialdehyde produced by the action of strictosidine p-D-glucosidase. This reactive intermediate is converted by uncharacterized enzymes into the major corynanthe, iboga, and aspidosperma skeletons that are elaborated into die several hundred alkaloids found in Catharanthns roseus. Since the biosynthesis of strictosidine appears to occur within plant vacuoles, there has been much speculation, but little is known, about the factors that regulate the accumulation of strictosidine within the vacuole, or which trigger its mobilization for further elaboration. It is well known that glycosides of different natural product classes are located within plant vacuoles. 

Figure 2.12 A hypothetical view of compartmentation of indole alkaloid biosynthesis in Catharanthus roseus. Enzymes located with dashed arrows are hypothetical and circles indicate membrane associated enzymes (after Meijer et at, 1 993b). Cl OH, geraniol-1 0-hydroxylase NMT, 5-adenosyl-L-methionine 11 -methoxy 2,16-dihydro-16-hydroxytabersonine N-methyltransferase DAT, acetylcoenzyme A deacetylvindoline 1 7-0-acetyltransferase OHT, 2-oxyglutarate-dependent dioxygenase SSpC, strictosidine-((3)-glucosidase SSS, strictosidine synthase.

The following step in the biosynthesis of the TIAs consists in the deglycosylation of strictosidine by strictosidine p-glucosidase (SGD) to form the strictosidine aglycone, which is an unstable product rapidly transformed into 4,21-dehydrogeissoschizine (Scheme 4.2). SGD is a glycoprotein localized in the endoplasmic reticulum and is highly specific for strictosidine [21]. This enzyme... 

Fig. 8.7 Biosynthetic pathway for monoteipenoid indole alkaloid (MIA) biosynthesis in plants. TDC tryptophan decarboxylase, STR strictosidine synthase, SGD strictosidine -o-glucosidase, T16H tabersonine 16-hydroxylase, D4H desacetoxyvindolme 4-hydroxylase, DAT deacetylvindoline 4-O-acetyltransferase (Adopted from Ref. [3])...

Figure 4.9 Biosynthesis of monoterpenoid indole alkaloids. Enzyme abbreviations TDC, tryptophan decarboxylase STR, strictosidine synthase SGD, strictosidine f-d-glucosidase T16H, tabersonine 16-hydroxylase D4H, desacetoxyvindoline 4-hydroxylase DAT, deacetylvindoline 4-O-acetyltransferase.

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