Carotenoid biosynthesis in intraerythrocytic stages of Plasmodium falciparum.
Carotenoids are widespread lipophilic pigments synthesized by all photosynthetic organisms and some nonphotosynthetic fungi and bacteria. All carotenoids are derived from the C40 isoprenoid precursor geranylgeranyl pyrophosphate, and their chemical and physical properties are associated with light absorption, free radical scavenging, and antioxidant activity. Carotenoids are generally synthesized in well defined subcellular organelles, the plastids, which are also present in the phylum Apicomplexa, which comprises a number of important human parasites, such as Plasmodium and Toxoplasma. Recently, it was demonstrated that Toxoplasma gondii synthesizes abscisic acid. We therefore asked if Plasmodium falciparum is also capable of synthesizing carotenoids. Herein, biochemical findings demonstrated the presence of carotenoid biosynthesis in the intraerythrocytic stages of the apicomplexan parasite P. falciparum. Using metabolic labeling with radioisotopes, in vitro inhibition tests with norflurazon, a specific inhibitor of plant carotenoid biosynthesis, the results showed that intraerythrocytic stages of P. falciparum synthesize carotenoid compounds. A plasmodial enzyme that presented phytoene synthase activity was also identified and characterized. These findings not only contribute to the current understanding of P. falciparum evolution but shed light on a pathway that could serve as a chemotherapeutic target.
Tonhosolo
Renata
R
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000, São Paulo, SP, Brazil.
D'Alexandri
Fabio L
FL
de Rosso
Veridiana V
VV
Gazarini
Marcos L
ML
Matsumura
Miriam Y
MY
Peres
Valnice J
VJ
Merino
Emilio F
EF
Carlton
Jane M
JM
Wunderlich
Gerhard
G
Mercadante
Adriana Z
AZ
Kimura
Emília A
EA
Katzin
Alejandro M
AM
D000818:Animals; D002338:Carotenoids / Q000378:metabolism*; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000469:parasitology*; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008288:Malaria / Q000628:therapy; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D010963:Plasmodium falciparum / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry; D014122:Toxoplasma / Q000378:metabolism
D006540:Herbicides; D011724:Pyridazines; D013729:Terpenes; D002338:Carotenoids; C008677:norflurazone