The polyamines putrescine, spermidine and spermine play an essential role in 
cell differentiation and proliferation. Inhibition of the rate-limiting enzymes 
of polyamine biosynthesis, ornithine decarboxylase (ODC) and 
S-adenosylmethionine decarboxylase (AdoMetDC), has been proposed as a 
therapeutic strategy against cancer and parasitic infections. In the case of 
Plasmodium falciparum, the causative agent of malaria tropica, this approach is 
especially interesting, because here both key enzymes, ODC and AdoMetDC, are 
combined in a bifunctional protein, ODC/AdoMetDC. This arrangement has not been 
found in any other organism investigated so far. We report the cloning and 
recombinant expression of the ODC domain of P. falciparum in Escherichia coli. 
First, we expressed the mere recombinant ODC domain (rPfODC). Secondly, we 
expressed the recombinant ODC domain in conjunction with the preceding part of 
the hinge region of the bifunctional ODC/AdoMetDC (rPfHinge-ODC). K(m) values 
for L-ornithine were 47.3 microM for the rPfHinge-ODC and 161. 5 microM for the 
rPfODC. Both recombinant enzymes were inhibited by putrescine, but the K(i) 
value for the rPfHinge-ODC was 50.4 microM (IC(50)=157 microM), whereas the 
IC(50) for the rPfODC was 500 microM. Spermidine was a weak inhibitor in both 
cases. alpha-Difluoromethylornithine inhibited the rPfHinge-ODC with a K(i) 
value of 87.6 microM. For two novel ODC inhibitors, CGP52622A and CGP54619A, the 
K(i) values of the rPfHinge-ODC were in the nanomolar range.