Cathenamine reductase

The formation of ajmalicine from the carbinolamine or cathenamine requires a reduction. Hemscheidt (217) and Stdckigt et al. (222) described an enzyme cathenamine reductase (CR), which used cathenamine as substrate and NADPH as cofactor, yielding ajmalicine and 19-epi-ajmalicine. Hemscheidt and Zenk (223) reported partial purification of an NADPH-dependent tetrahydroalstonine synthase (THAS) from C. roseus cell cultures. This enzyme only yields tetrahydroalstonine, and the substrate was the iminium form of cathenamine. The Km for this substrate is 62 /nAf. The molecular mass of the enzyme was estimated to be 81 kDa. 

Dehydrogeissoschizine may also be converted to cathenamine in a reaction catalyzed by cathenamine synthase (CS) [24]. This compound is the basis for the formation of ajmaUcine by the action of the enzyme cathenamine reductase (CR), and then, ajmalicine is thought to be oxidized to serpentine by class 111 peroxidases (Prx) localized in the vacuoles, with its production being strongly regulated by light (Scheme 4.4, [25]). 

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])... 

AjmaUcine is derived from hyptamine (partly from geraniol) via secologanin, strictosidine, and cathenamine. It has a Corynanthe skeleton from deglycosylated strictosidine [28]. AjmaUcine is synthesized in the cytosol by the action of cathenamine reductase on cathenamine facilitated by NADPH activity [32]. The biosynthesis of ajmalicine has been studied with reference to improving the cmitent by various biotechnological approaches (Fig. 20.4). The regulatirai per se of ajmalicine production has not been explored in larger detail. 

Ajmalicine (raubasine) affects smooth muscle function and is used to help prevent strokes (93), and tetrahydroalstonine exhibits antipsychotic properties (Fig. 2d) (94). These compounds are found in a variety of plants, including C. roseus and R. serpentina. A partially purified NADPH-dependent reductase isolated from a tetrahydroalstonine that produces a C. roseus cell line was shown to catalyze the conversion of cathenamine, a spontaneous reaction product that results after strictosidine deglycosylation, to tetrahydroalstonine in vitro (95). A second C. roseus cell line contains an additional reductase that produces ajmalicine. Labeling studies performed with crude C. 

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