Abstract
Malaria remains the world's most devastating tropical infectious disease with as many as 40% of the world population living in risk areas. The widespread resistance of Plasmodium parasites to the cost-effective chloroquine and antifolates has forced the introduction of more costly drug combinations, such as Coartem®. In the absence of a vaccine in the foreseeable future, one strategy to address the growing malaria problem is to identify and characterize new and durable antimalarial drug targets, the majority of which are parasite proteins. Biochemical and structure-activity analysis of these proteins is ultimately essential in the characterization of such targets but requires large amounts of functional protein. Even though heterologous protein production has now become a relatively routine endeavour for most proteins of diverse origins, the functional expression of soluble plasmodial proteins is highly problematic and slows the progress of antimalarial drug target discovery. Here the status quo of heterologous production of plasmodial proteins is presented, constraints are highlighted and alternative strategies and hosts for functional expression and annotation of plasmodial proteins are reviewed.
Highlights
Malaria is a devastating disease and its long-term control and eradication are still a long way off
This review highlights the properties that have been associated with difficult-to-express plasmodial proteins and provides insights into the variety of options available for the heterologous expression of malaria parasite proteins for structural and functional annotation studies
(page number not for citation purposes) http://www.malariajournal.com/content/7/1/197 latter may be compromized by spurious and unpredictable O-glycosylation of the heterologous protein, as well as the formation of disulphide bond conformers with reduced protective immunogenicity [112,113]. It appears that the use of Pichia pastoris may improve heterologous protein yield, compared with S. cerevisiae, and levels of 30 mg/L to more than 1 g/L of purified protein have consistently been reported, especially when combined with batch-fed fermentation [113,114,115,116,117,118,119,120,121]
Summary
Malaria is a devastating disease and its long-term control and eradication are still a long way off. The redox environment and co-factors in the yeast secretory pathway should enhance correct folding, solubility and intra-molecular disulphide bonding of vaccine proteins that rely critically on conformational epitopes to generate a protective immune response; the http://www.malariajournal.com/content/7/1/197 latter may be compromized by spurious and unpredictable O-glycosylation of the heterologous protein, as well as the formation of disulphide bond conformers with reduced protective immunogenicity [112,113] It appears that the use of Pichia pastoris may improve heterologous protein yield, compared with S. cerevisiae, and levels of 30 mg/L to more than 1 g/L of purified protein have consistently been reported, especially when combined with batch-fed fermentation [113,114,115,116,117,118,119,120,121]. Inverse correlations were observed between soluble protein production and protein size, frequency of low-complexity regions and pI of the proteins
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