In the human malaria parasite Plasmodium falciparum, polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase

The polyamines putrescine, spermidine, and spermine are crucial for cell di fferentiation and proliferation. Interference with polyamine biosynthesis b y inhibition of the rate-limiting enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) has been discussed as a pote ntial chemotherapy of cancer and parasitic infections. Usually both enzymes are individually transcribed and highly regulated as monofunctional protei ns. We have isolated a cDNA from the malaria parasite Plasmodium falciparum that encodes both proteins on a single open reading frame, with the AdoMet DC domain in the N-terminal region connected to a C-terminal ODC domain by a hinge region. The predicted molecular mass of the entire transcript is 16 6 kDa. The ODC/AdoMetDC coding region was subcloned into the expression vec tor pASK IBA3 and transformed into the AdoMetDC- and ODC-deficient Escheric hia coli cell line EWH331. The resulting recombinant protein exhibited both AdoMetDC and ODC activity and co-eluted after gel filtration on Superdex S -200 at similar to 333 kDa, which is in good agreement with the molecular m ass of similar to 326 kDa determined for the native protein from isolated P . falciparum, SDS-polyacrylamide gel electrophoresis analysis of the recomb inant ODC/AdoMetDC revealed a heterotetrameric structure of the active enzy me indicating processing of the AdoMetDC domain. The data presented describ e the occurrence of a unique bifunctional ODC/AdoMetDC in P. falciparum, an organization which is possibly exploitable for the design of new antimalar ial drugs.