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Description:
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Cryptosporidium parvum is widely known for outbreaks within the immunocompetent population , as well its sometimes excruciating effects as an opportunistic agent in AIDS patients . Our understanding of the biology and host -parasite interactions of this parasitic protist is increasing at a rapid rate due to recent molecular and genetic advances . The topic of our research is in the area of C . parvum fatty acid metabolism , which is highly streamlined in this parasite . In addition to a type I fatty acid synthase (CpFAS1 ) , C . parvum also possesses an enormous type I polyketide synthase (CpPKS1 ) . Because of the size of this megasynthase , functional characterization of the complete enzyme is not possible . We have isolated and characterized the loading unit of CpPKS1 which contains an acyl -[acyl carrier protein (ACP )] ligase (AL ) and an ACP . This unit is responsible for the overall substrate selection and initiation of polyketide production . Our data show that CpPKS1 prefers long -chain fatty acids with the highest specificity for arachidic acid (C20 ) . Thus , the final polyketide product could contain as many as 34 carbons . Additionally , C . parvum possesses only a single fatty acid elongase . This family of enzymes serves a mechanism similar to FAS , and many have been found to be involved in de novo fatty acid synthesis in other organisms . After expressing this membrane protein in human cells , we have determined that it too prefers long -chain fatty acyl -CoAs which undergo only one round of elongation . This is in contrast to members of this enzyme family in other organisms that can initiate de novo synthesis from two - or four -carbon fatty acids via several rounds of elongation . Our lab has previously characterized the unique acyl -CoA binding protein (CpACBP1 ) from C . parvum . Molecular and biochemical data suggested that this enzyme may serve as a viable drug target . We have screened a library of known (and somewhat common ) compounds against CpACBP1 , and have isolated several potential compounds to be further examined for their ability to inhibit the growth of C . parvum . |