Polypeptide Manufacturing with SUMO

Polypeptides are commonly synthesized by traditional chemistry. There are a few disadvantages of chemical synthesis of polypeptides: 1) errors occur in sequence with certain amino acids during chemical synthesis, 2) not all chemically synthesized peptides fold correctly, and 3) yield of polypeptides decreases along with the length of the polypeptide. SUMO system has been proven as the best method for recombinant production of polypeptides, especially longer peptides.

Click to Read More: Benefits of SUMO

SUMO helps to:
1) Stabilize polypeptide to increase the yield
2) Encode desired N-terminal sequence
3) Ensure a correctly folded polypeptide due to SUMO chaperoning properties.

SUMO system is the most cost-effective way to manufacture growth hormones, glucagon-like polypeptides, and anti-microbial and industrial polypeptides. Contact LifeSensors to decrease the cost of goods for your polypeptide production. We will guide you about the best way to manufacture your polypeptide and transfer the manufacturing process to GMP sites.

The SUMO Tag

SUMO (Small Ubiquitin-like Modifier) is a member of the ubiquitin family, composed of a flexible N-terminal region followed by a ball-shaped ubiquitin-like fold. SUMO’s hydrophobic core improves correct folding of the fused polypeptides, and its hydrophilic surface keeps the partner protein soluble. SUMO protease recognizes SUMO structure to cleaves at the junction to generate desired N-terminus of the polypeptide.

Workflow schematic of TUBE proteomics

Figure 2: The Principle of the system. SUMO Protease cleaves the SUMO 6xHis tag to separate the expressed polypeptide. The 6xHis is used to assist in purification while SUMO or SUMOstar enhanced protein productions.

the protein structure of SUMO

Figure 1: The unique string and ball structure of SUMO allows for improved expression due to a hydrophilic outer surface and a hydrophobic core.

LifeSensors pioneered the application of SUMO system to enhance production of polypeptides as published by Marblestone et. Al, Protein Sci. 2006. SUMO system is superior to several other tags: 6xHis, Ubiquitin, MBP, GST, and TRX. More recent studies [1],[2],[3],[4],[5] have shown a range of applications through expression of antimicrobial, cytotoxic peptides, and anti-thrombotic peptides.

Removal of the polypeptide from the tag is costly or impossible due to the inability of the proteases to cleave and provide the desired amino acid sequence. LifeSensors’ SUMO proteases recognize the SUMO structure and does not discriminate between fused polypeptide cleavage sites by generating the desired N-terminal sequence. As shown in the table below (Table 1), the cost of enzymatic cleavage of polypeptide is a major factor that has been a hurdle in adopting recombinant methods for polypeptide production. LifeSensors has developed the most efficient SUMO protease to reduce the cost of goods. As shown in the table below, SUMO mediated manufacturing of the polypeptide is the most cost-effective method. We encourage inquiries to establish cost-effective pilot scale manufacturing of polypeptides. The manufacturing process can be seamlessly transferred to GMP facilities.

Workflow schematic of TUBE proteomics

Table 1: Cost comparison of common tag removal enzymes. *Cost is based on a 6-hour reaction time, **Cost is based on a 16-hour reaction time. LifeSensors’ SUMO Protease requires only a single hour of reaction time to achieve this price per mg of protein cleaving capability. SUMO protease is the most inexpensive process to remove the tag, decrease the cost of goods and increase the yield of the polypeptide.

Preview our Presentation on Peptide Production

Click for: Lifesensors' SUMO Publication Searchable Sheet

To use, simply utilize the drop down arrows in order to search for your target of interest or application category. Lifesensors SUMO technology has been utilized for the expression of many different targets and continues to be utilized worldwide.

[1] Ishida Y et al, AMB Express. 2016
[2] Islam, M.R., Plant Cell Rep, 2019
[3] Yang NJ et al, Front Immunol. 2021
[4] Derakhshani A et al, Int J Biol Macromol. 2020
[5] Kotál J et al, Int J Mol Sci. 2021

1.https://www.fishersci.com/shop/products/promega-protev-plus-protease-2/p-4389612
2.https://www.sigmaaldrich.com/US/en/product/sigma/ge27084601
3.https://www.neb.com/products/p8010-factor-xa-protease#Product%20Information_Properties%20&%20Usage
4.https://www.neb.com/products/p8070-enterokinase-light-chain#Product%20Information
5.https://lifesensors.com/product/sp4010-sumo-protease-1/

Lifesensors has pioneered SUMO technologies and discovery, and is looking forward to sharing these discoveries and applications with the greater pharmaceutical and biotech communities.

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