Enzymes cadaverine conversion

This pyridoxal-phosphate-dependent enzyme [EC 4.1.1.18] catalyzes the conversion of L-lysine to form cadaverine and carbon dioxide. 5-Hydroxy-L-lysine can also be decarboxylated by this enzyme. 

The crude enzyme preparation was found to catalyse the conversion of cadaverine (16) mainly into 17-oxosparteine (27) in the presence of pyruvic acid. The pyruvic acid served as a receptor for the amino-groups of (16) in a transamination reaction, having manifestly a close relationship to alkaloid formation.11 Diamine oxidase activity might have been expected to account for the... 

Quinolizidine Alkaloids.—Important new information (cf. Vol. 11, p. 4) has been obtained on the biosynthesis of quinolizidine alkaloids such as lupanine (27) in experiments with enzyme preparations from Lupinus polyphyllus cell suspension cultures26 and with chloroplasts.27 These alkaloids are formed from three molecules of lysine by way of cadaverine (25),1,2 and the enzymic evidence26,27 is that conversion of cadaverine into these alkaloids occurs without release of intermediates until 17-oxosparteine (26) is generated the enzyme is a transaminase and not a diamine oxidase. 

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. 

In further consideration of the biosynthesis of the piperidine alkaloids the question of the significance of the incorporation of cadaverine must be answered. Accordingly further research has been directed to this point and it has been shown that cadaverine is a normal component of S. acre, that it is a specific precursor of sedamine (20), and that it is formed from lysine at the same time as sedamine. It follows then that any scheme for the biosynthesis of the piperidine alkaloids which does not accommodate cadaverine as a normal component is unrealistic An eminently reasonable hypothesis which fits all the evidence is shown in Scheme 1 it was anticipated in last year s Report. For those alkaloids derived from lysine without the intervention of a symmetrical intermediate, cadaverine formed by decarboxylation of lysine must remain enzyme-bound and therefore unsymmetrical. Exogenous cadaverine enters the pathway at this point by absorption on to the enzyme to give (29). In order to explain the incorporation of lysine into some alkaloids by way of a symmetrization step it is necessary only to postulate equilibration of bound with unbound cadaverine. The proposal that pyridoxal phosphate is involved in this pathway is more than mechanistically attractive, for L-lysinedecarboxylase (EC 4.1.1.18, L-lysine carboxy-lyase) and diamine oxidase [EC 1.4.3.6, diamine oxygen oxidoreductase (deaminating)], the two enzymes whose participation in the conversion of lysine into A -piperideine (30) is likely, both require pyridoxal phosphate as a co-factor. 

This study with the chirally labelled cadaverines brings to light an apparent anomaly. Decarboxylation of L-[2- H]lysine by the enzyme from B. cadaveris affords [lB- H]cadaverine. When this material is converted into N-methyl-pelletierine (22) and AT-methylallosedridine in S. sarmentosum the tritium destined for C-2 is lost. On the other hand conversion of lysine into the sedamine in S. acre results in the retention of tritium originally present at C-l The simplest explanation of this is that the protonation of (28) in the micro-organism and the plants proceeds with opposite stereochemistry. 

L-Lysine and cadaverine serve as precursors for the majority of piperidine alkaloids. The experimental results have been interpreted in terms of an attractive series of pyridoxal-linked intermediates derivable independently from both precursors see Scheme 1. The transformation of cadaverine into alkaloids involves stereospecific removal of one of the protons attached to C-1 (pro-S hydrogen) and probably involves a diamine oxidase cf. refs. 5 and 6. Examination of the diamine-oxidase-catalysed oxidation of cadaverine, with enzyme from hog kidney, and analysis by an excellent n.m.r. method, has shown that this reaction also involves removal of the 1-pro-5 proton from the diamine pea seedling diamine oxidase has been found to effect the conversion of benzylamine into benzaldehyde with similar stereochemistry. ... 

---