Dictyostelium discoideum—a promising expression system for the production of eukaryotic proteins

Abstract

In general, four different expression systems, namely, bacterial, yeast, baculovirus, and mammalian, are widely used for the overproduction of biochemical enzymes and therapeutic proteins. Clearly, bacterial expression systems offer ease of maneuverability with respect to large-scale production of recombinant proteins, while, a baculovirus expression system ensures proper protein modifications, processing, and refolding of complex proteins. Despite these advantages, mammalian cells remain the preferred host for many eukaryotic proteins of pharmaceutical importance, particularly, those requiring post-translational modifications. Recently, the single-celled slime mold, Dictyostelium discoideum (Dd), has emerged as a promising eukaryotic host for the expression of a variety of heterologous recombinant eukaryotic proteins. This organism possesses the complex cellular machinery required for orchestrating post-translational modifications similar to the one observed in higher eukaryotes. This review summarizes the advantages and disadvantages of Dictyostelium as an alternate system compared to other well-established expression systems. The key lessons learned from the expression of human recombinant proteins in this system are reviewed. Also, the strengths, weaknesses, and challenges associated with industrial-scale production of proteins in Dd expression system are discussed.

Effective Isotope Labeling of Proteins in a Mammalian Expression System

“…D. discoideum has the potential to be an attractive expression system because isotopically enriched bacteria can be used as a nutrient source, thereby reducing the overall cost of isotopic labeling. However, heterologous expression of proteins in D. discoideum has its own challenges (Arya, Bhattacharya, & Saini, 2008); to date, there is only one published report describing successful production of an isotopically labeled protein using this system (Swarbrick et al, 2009). Thus, expression of isotopically enriched eukaryotic proteins in their stable, correctly folded form remains a bottleneck for spectroscopic characterization of many proteins.…”

Influence of culture medium on the production of eif antigen from Leishmania chagasi in recombinant Escherichia coli

“…Proteins such as interferons, interleukin and growth hormones are some of the recombinant proteins successfully expressed in E. coli (4). However, E. coli has a number of limitations in its expression system, including inability to carry out post-translational changes, common in eukaryotic cells, lack of secretion system for efficient release of the recombinant protein into the culture medium (1). Protein *Corresponding Author.…”

Production of recombinant proteins from protozoan parasites

“…T. thermophila is the most advanced [54]. In the case of Dictyostelium , which has recently been proposed as an alternative expression system for eukaryotic proteins ([60]) it is available at the Dictyostelium consortium (http://www.nih.gov/science/models/d_discoideum/). The P. marinus system is under development at the corresponding author laboratory.…”

“…Because of its multiple advantages, which include axenic in vitro culture in synthetic media, Dictyostelium has been recently proposed as an alternative expression system for eukaryotic proteins (reviewed in Ref. [60]). As an alternative subunit vaccine against malaria, the Plasmodium recombinant CSP anchored to the surface of Dictyostelium , elicited antibodies against two different regions of the target protein [61].…”