SUMO Technology and Difficult to Express Protein

Fusion with SUMO (Small Ubiquitin-like Modifier) has revolutionized the way difficult to express proteins are made

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Fusion with SUMO (Small Ubiquitin-like Modifier) has revolutionized the way difficult to express proteins are made. The SUMO tag offers advantages over traditional expression methods. Mechanisms and benefits of SUMO mediated enhanced expressions include:

Chaperoning properties of SUMO dramatically enhance translation of proteins/polypeptides
Presence of globular protease resistant SUMO domain stabilizes proteins
The most efficient SUMO protease reduces the cost of native protein production
SUMO protease cleaves any amino acid sequence at the junction generating desired N-termini, especially important for cytokine, growth factors and chemokine to restore biological activity

Enhanced Expression

Dramatically enhances protein expression while maintaining protein function

Native N-Terminus

Engineered SUMO proteases will result in intact native n-terminus

SUMOpro Technology

Ideal for enhanced expression, increased solubility and native folding in E.coli

SUMOpro3 System

Designed with human SUMO tag for mammalian expression suitable for proteins that require post translational modifications

SUMOstar Technology

For use in eukaryotic hosts – designed to resist endogenous proteases

Distinction Between SUMOpro and SUMOstar

Expression of Therapeutic Proteins in Mammalian Cells

SUMO pathway is conserved in eukaryotic cells. E.coli lacks SUMO pathway and SUMO proteases. Unlike SUMOpro which is used to express SUMO fusion in E.coli, native SUMO fusions are rapidly cleaved in eukaryotic cells. To circumvent this problem and to take advantage of chaperoning properties of SUMO in mammalian cells, the SUMO tag was engineered. The engineered SUMO is not cleaved, thus preserving enhanced protein production properties of SUMO. The engineered SUMO is called SUMOstar. SUMOstar fusions are not cleaved by eukaryotic SUMO proteases. The isolated SUMOstar fusions from eukaryotic cells can be efficiently cleaved by SUMOstar protease in vitro.

Growing Applications

Application of SUMOpro and SUMOstar continues to increase. ~1000 scholarly papers are published.

Application of SUMO System across the Biological Spectrum

SUMOpro technology is ideal for enhanced expression, increased solubility, and native folding in E.coli. The SUMOstar system presents similar advantages for native protein expression in mammalian cells.

Chemical synthesis of polypeptides is prone to errors. Not all chemically synthesized peptides fold correctly, and the yield of polypeptides decreases along with the length of the polypeptide.

E.coli provides an attractive platform to express animal vaccines at a low cost. The SUMO system provides the capability to increase yield and serves as a tool to rapidly purify the antigen.

Although mammalian cells have proven to be workhorses for antibody production, engineered single chain antibodies (Nanobodies) are especially difficult to manufacture in mammalian cells. SUMOpro is an inexpensive method for Nanobody production.

Despite the strong promoters, many genes are not expressed well in recombinant adeno associated viruses (rAAV). LifeSensors has established a human SUMOstar based system that allows under expressed or non-expressed genes to be delivered as SUMOstar fusion between rAAV ITR containing plasmids.