List of recombinant proteins

The following is a list of notable proteins that are produced from recombinant DNA, using biomolecular engineering.[1] In many cases, recombinant human proteins have replaced the original animal-derived version used in medicine. The prefix "rh" for "recombinant human" appears less and less in the literature. A much larger number of recombinant proteins is used in the research laboratory. These include both commercially available proteins (for example most of the enzymes used in the molecular biology laboratory), and those that are generated in the course specific research projects.

Human recombinants that largely replaced animal or harvested from human types

Medicinal applications

• Human growth hormone (rHGH): Humatrope from Lilly and Serostim from Serono replaced cadaver harvested human growth hormone
• human insulin (BHI): Humulin from Lilly and Novolin from Novo Nordisk among others largely replaced bovine and porcine insulin for human therapy. Some prefer to continue using the animal-sourced preparations, as there is some evidence that synthetic insulin varieties are more likely to induce hypoglycemia unawareness. Remaining manufacturers of highly purified animal-sourced insulin include the U.K.'s Wockhardt Ltd. (headquartered in India), Argentina's Laboratorios Beta S.A., and China's Wanbang Biopharma Co.
• Follicle-stimulating hormone (FSH) as a recombinant gonadotropin preparation replaced Serono's Pergonal which was previously isolated from post-menopausal female urine
• Factor VIII: Kogenate from Bayer replaced blood harvested factor VIII

Research applications

• Ribosomal proteins: For the studies of individual ribosomal proteins, the use of proteins that are produced and purified from recombinant sources[2][3][4][5] has largely replaced those that are obtained through isolation.[6][7] However, isolation is still required for the studies of the whole ribosome.[8][9]
• Lysosomal proteins: Lysosomal proteins are difficult to produce recombinantly due to the number and type of post-translational modifications that they have (e.g. glycosylation). As a result, recombinant lysosomal proteins are usually produced in mammalian cells.[10] Plant cell culture was used to produce FDA aproved glycosilated lysosmal protein-drug, and additional drug candidates.[11] Recent studies have shown that it may be possible to produce recombinant lysosomal proteins with microorganisms such as Escherichia coli and Saccharomyces cerevisiae.[12] Recombinant lysosomal proteins are used for both research and medical applications, such as enzyme replacement therapy.[13]

Human recombinants with recombination as only source

Medicinal applications

• Erythropoietin (EPO):[14] Epogen from Amgen
• Granulocyte colony-stimulating factor (G-CSF): filgrastim sold as Neupogen from Amgen; pegfilgrastim sold as Neulasta
• alpha-galactosidase A: Fabrazyme by Genzyme[15]
• alpha-L-iduronidase: (rhIDU; laronidase) Aldurazyme by BioMarin Pharmaceutical and Genzyme
• N-acetylgalactosamine-4-sulfatase (rhASB; galsulfase): Naglazyme by BioMarin Pharmaceutical
• Dornase alfa, a DNase sold under the trade name Pulmozyme by Genentech
• Tissue plasminogen activator (TPA) Activase by Genentech
• Glucocerebrosidase: Ceredase by Genzyme
• Interferon (IF) Interferon-beta-1a: Avonex from Biogen Idec; Rebif from Serono; Interferon beta-1b as Betaseron from Schering.[16] It is being investigated for the treatments of diseases including Guillain-Barré syndrome[17] and multiple sclerosis.[18]
• Insulin-like growth factor 1 (IGF-1)[19]
• Rasburicase, a Urate Oxidase analog sold as Elitek from Sanofi[20]

Animal recombinants

Medicinal applications

• Bovine somatotropin (bST)
• Porcine somatotropin (pST)
• Bovine Chymosin

Bacterial recombinants

Industrial applications

• Xylanases[21]
• Proteases, which have found applications in both the industrial (such as the food industry)[22] and domestic settings.[23]

Viral recombinants

Medicinal applications

• Envelope protein of the hepatitis B virus marketed as Engerix-B by SmithKline Beecham
• HPV Vaccine proteins

Plant recombinants

Research applications

• Polyphenol oxidases (PPOs): These include both catechol oxidases and tyrosinases.[24][25][26][27][28] In additional to research, PPOs have also found applications as biocatalysts.[29]
• Cystatins are proteins that inhibit cysteine proteases.[30][31][32][33] Research are ongoing to evaluate the potential of using cystatins in crop protection to control herbivorous pests and pathogens.[34]

Industrial applications

• Laccases have found a wide range of application, from food additive and beverage processing to biomedical diagnosis, and as cross‐linking agents for furniture construction or in the production of biofuels.[29][35][36][37][38]

See also

• Protein production
• Gene expression
• Protein purification
• Host cell protein

References

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2. Danilo Correddu, José de Jesús Montaño López, Praveen G. Vadakkedath, Amy Lai, Jane I. Pernes, Paris R. Watson, Ivanhoe K. H. Leung (2019). "An improved method for the heterologous production of soluble human ribosomal proteins in Escherichia coli". Sci. Rep. 9: 8884. doi:10.1038/s41598-019-45323-8. PMC 6586885. PMID 31222068.CS1 maint: multiple names: authors list (link)
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10. Damiano Migani, Christopher Mark Smales, Daniel G. Bracewell (2017). "Effects of lysosomal biotherapeutic recombinant protein expression on cell stress and protease and general host cell protein release in Chinese hamster ovary cells". Biotechnol. Prog. 33: 666–676. doi:10.1002/btpr.2455. PMC 5485175. PMID 28249362.CS1 maint: multiple names: authors list (link)
11. Tekoah, Yoram; Shulman, Avidor; Kizhner, Tali; Ruderfer, Ilya; Fux, Liat; Nataf, Yakir; Bartfeld, Daniel; Ariel, Tami; Gingis-Velitski, Svetlana; Hanania, Uri; Shaaltiel, Yoseph (October 2015). "Large-scale production of pharmaceutical proteins in plant cell culture-the protalix experience". Plant Biotechnology Journal. 13 (8): 1199–1208. doi:10.1111/pbi.12428.
12. Ángela J. Espejo-Mojica, Carlos J. Alméciga-Díaz, Alexander Rodríguez, Ángela Mosquera, Dennis Díaz, Laura Beltrán, Sergio Díaz, Natalia Pimentel, Jefferson Moreno, Jhonnathan Sánchez, Oscar F. Sánchez, Henry Córdoba, Raúl A. Poutou-Piñales, Luis A. Barrera (2015). "Human recombinant lysosomal enzymes produced in microorganisms". Mol. Genet. Metab. 116: 13–23. doi:10.1016/j.ymgme.2015.06.001. PMID 26071627.CS1 maint: multiple names: authors list (link)
13. Melani Solomon, Silvia Muro (2017). "Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives". Adv. Drug Deliv. Rev. 118: 109–134. doi:10.1016/j.addr.2017.05.004. PMC 5828774. PMID 28502768.
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24. Yu Li, Mark-Anthony McLarin, Martin J. Middleditch, Stuart J. Morrow, Paul A. Kilmartin, Ivanhoe K. H. Leung (2019). "An approach to recombinantly produce mature grape polyphenol oxidase". Biochimie. doi:10.1016/j.biochi.2019.07.002.CS1 maint: multiple names: authors list (link)
25. Ala eddine Derardja, Matthias Pretzler, Ioannis Kampatsikas, Malika Barkat, Annette Rompel (2017). "Purification and Characterization of Latent Polyphenol Oxidase from Apricot (Prunus armeniaca L.)". J. Agric. Food Chem. 65: 8203–8212. doi:10.1021/acs.jafc.7b03210. PMC 5609118. PMID 28812349.CS1 maint: multiple names: authors list (link)
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35. Diana M. Mate, Miguel Alcalde (2017). "Laccase: a multi‐purpose biocatalyst at the forefront of biotechnology". Microb. Biotechnol. 10: 1457–1467. doi:10.1111/1751-7915.12422. PMC 5658592. PMID 27696775.
36. Fabio Tonin, Elena Rosini, Luciano Piubelli, Antonio Sanchez-Amat,Loredano Pollegioni (2016). "Different recombinant forms of polyphenol oxidase A, a laccase from Marinomonas mediterranea". Protein Expr. Purif. 123: 60–69. doi:10.1016/j.pep.2016.03.011. PMID 27050199.CS1 maint: multiple names: authors list (link)
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External links

• Laboratorios Beta S.A website
• CP Pharma/Wockhardt UK website