Oxosparteine synthase

This pathway clearly proves that the first quinolizidine alkaloid to be synthesized is (—) lupinine (two cycling alkaloids) and subsequently both (+)-lupanine and (-)-sparteine. This is a new approach to the synthesis of this type of alkaloids because in the older literature just four cycling alkaloids (lupanine and sparteine) were mentioned as the first synthesized molecules . In the cadaverine conversion, the participation of diamine oxidase is more reliable than the oxosparteine synthase mentioned by some older studies °. 

The enzyme, i.e. lysine decarboxylase, that is required for the conversion of lysine into cadaverine, and thus the first step of alkaloid biosynthesis, has been isolated from chloroplasts of L. polyphyllus,28 Like the majority of amino-acid decarboxylases, this enzyme is dependent on pyridoxal 5 phosphate. Its activity was found not to be affected by the presence or absence of quinolizidine alkaloids. Control of the enzyme by simple product feedback inhibition therefore seems unlikely. The operational parameters of this enzyme resemble those of the 17-oxosparteine synthase. Co-operation between the two enzymes would explain why cadaverine is almost undetectable in vivo. 

We propose the biosynthetic pathway of the carbon framework of matrine as shown in Fig. 4. This scheme also indicates the pathway for the formation of sparteine and lupanine. The former part of this scheme was proposed by Wink et al. [63], with minor modification by Leete [64], from the in vitro experiments using isolated chloroplasts of leaves of Lupinus. They postulated the presence of 17-oxosparteine as the first key intermediate for the formation of lupanine and sparteine [63]. However, this hypothesis involving 17-oxosparteine synthase was not confirmed by the tracer experiments using and independently conducted by the groups of Spenser [65, 66] and Robins [67]. They, in turn, hypothesized the pathway involving the diiminium cation (73) as the tetracyclic intermediate [68, 69]. The postulation of the presence of this reactive intermediate is consistent with the results of isotope incorporation into lupanine and sparteine. The biosynthetic scheme of matrine can be also drawn by involving the electronically equivalent diiminium cation (76) preceded by additional 1,3-hydride shift or imine-enamine isomerization (74 75). All these reactions take... 

More recent enzymatic evidence showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme-bound intermediates without the generation of any free intermediates. The enzyme 17-oxosparteine synthase requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine (Figure 7.33) [64]. 

Fig. 235. Proposed scheme for the biosynthesis of sparteine 1 17-Oxosparteine synthase...

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