List of recombinant proteins explained

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-approved glycosylated lysosomal 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] [29]} In additional to research, PPOs have also found applications as biocatalysts.^[30]
• Cystatins are proteins that inhibit cysteine proteases.^{[31] [32] [33] [34]} Research are ongoing to evaluate the potential of using cystatins in crop protection to control herbivorous pests and pathogens.^[35]

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.^{[36] [37] [38] [39]}
• The tyrosinase‐induced polymerization of peptides offers facile access to artificial mussel foot protein analogues. Next generation universal glues can be envisioned that perform effectively even under rigorous seawater conditions and adapt to a broad range of difficult surfaces.^[40]

See also

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

External links

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

Notes and References

1. Young CL, Britton ZT, Robinson AS . Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications . en . Biotechnology Journal . 7 . 5 . 620–34 . May 2012 . 22442034 . 10.1002/biot.201100155 . 35209677 .
2. Correddu D, Montaño López JJ, Vadakkedath PG, Lai A, Pernes JI, Watson PR, Leung IK . An improved method for the heterologous production of soluble human ribosomal proteins in Escherichia coli . Scientific Reports . 9 . 1 . 8884 . June 2019 . 31222068 . 6586885 . 10.1038/s41598-019-45323-8 . 2019NatSR...9.8884C .
3. Parakhnevitch NM, Malygin AA, Karpova GG . Recombinant human ribosomal protein S16: expression, purification, refolding, and structural stability . Biochemistry. Biokhimiia . 70 . 7 . 777–81 . July 2005 . 16097941 . 10.1007/s10541-005-0183-3 . 9910425 .
4. Malygin A, Baranovskaya O, Ivanov A, Karpova G . Expression and purification of human ribosomal proteins S3, S5, S10, S19, and S26 . Protein Expression and Purification . 28 . 1 . 57–62 . March 2003 . 12651107 . 10.1016/S1046-5928(02)00652-6 .
5. Tchórzewski M, Boguszewska A, Abramczyk D, Grankowski N . Overexpression in Escherichia coli, purification, and characterization of recombinant 60S ribosomal acidic proteins from Saccharomyces cerevisiae . Protein Expression and Purification . 15 . 1 . 40–7 . February 1999 . 10024468 . 10.1006/prep.1998.0997 .
6. Collatz E, Ulbrich N, Tsurugi K, Lightfoot HN, MacKinlay W, Lin A, Wool IG . Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 40 S ribosomal subunit proteins Sa, Sc, S3a, S3b, S5', S9, S10, S11, S12, S14, S15, S15', S16, S17, S18, S19, S20, S21, S26, S27', and S29 . The Journal of Biological Chemistry . 252 . 24 . 9071–80 . December 1977 . 10.1016/S0021-9258(17)38346-1 . 925037 . free .
7. Fogel S, Sypherd PS . Extraction and isolation of individual ribosomal proteins from Escherichia coli . Journal of Bacteriology . 96 . 2 . 358–64 . August 1968 . 4877123 . 252306 . 10.1128/JB.96.2.358-364.1968 .
8. Book: Mehta P, Woo P, Venkataraman K, Karzai AW . Ribosome Purification Approaches for Studying Interactions of Regulatory Proteins and RNAs with the Ribosome . Bacterial Regulatory RNA . en . Methods in Molecular Biology . 905 . 273–89 . 2012 . 22736011 . 10.1007/978-1-61779-949-5_18 . 4607317 . 978-1-61779-948-8 .
9. Belin S, Hacot S, Daudignon L, Therizols G, Pourpe S, Mertani HC, Rosa-Calatrava M, Diaz JJ . 6 . Purification of ribosomes from human cell lines . en . Current Protocols in Cell Biology . Chapter 3 . Unit 3.40 . December 2010 . 21154551 . 10.1002/0471143030.cb0340s49 . 23908342 .
10. Migani D, Smales CM, Bracewell DG . Effects of lysosomal biotherapeutic recombinant protein expression on cell stress and protease and general host cell protein release in Chinese hamster ovary cells . en . Biotechnology Progress . 33 . 3 . 666–676 . May 2017 . 28249362 . 10.1002/btpr.2455 . 5485175 .
11. Tekoah Y, Shulman A, Kizhner T, Ruderfer I, Fux L, Nataf Y, Bartfeld D, Ariel T, Gingis-Velitski S, Hanania U, Shaaltiel Y . 6 . Large-scale production of pharmaceutical proteins in plant cell culture-the Protalix experience . Plant Biotechnology Journal . 13 . 8 . 1199–208 . October 2015 . 26102075 . 10.1111/pbi.12428 . free .
12. Espejo-Mojica ÁJ, Alméciga-Díaz CJ, Rodríguez A, Mosquera Á, Díaz D, Beltrán L, Díaz S, Pimentel N, Moreno J, Sánchez J, Sánchez OF, Córdoba H, Poutou-Piñales RA, Barrera LA . 6 . Human recombinant lysosomal enzymes produced in microorganisms . en . Molecular Genetics and Metabolism . 116 . 1–2 . 13–23 . 2015 . 26071627 . 10.1016/j.ymgme.2015.06.001 .
13. Solomon M, Muro S . Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives . en . Advanced Drug Delivery Reviews . 118 . 109–134 . September 2017 . 28502768 . 10.1016/j.addr.2017.05.004 . 5828774 .
14. Book: Inoue N, Takeuchi M, Ohashi H, Suzuki T . Biotechnology Annual Review Volume 1 . The production of recombinant human erythropoietin . en . 1 . 297–313 . 1995 . 9704092 . 10.1016/S1387-2656(08)70055-3 . 9780444818904 .
15. Baigent G . Recombinant Interleukin-2 (rIL-2), aldesleukin . en . Journal of Biotechnology . 95 . 3 . 277–80 . May 2002 . 12007868 . 10.1016/S0168-1656(02)00019-6 .
16. Munafo A, Trinchard-Lugan I, Nguyen TX, Buraglio M . Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta-1a after intramuscular and subcutaneous administration . en . European Journal of Neurology . 5 . 2 . 187–193 . March 1998 . 10210831 . 10.1046/j.1468-1331.1998.520187.x . 221594104 .
17. Pritchard J, Gray IA, Idrissova ZR, Lecky BR, Sutton IJ, Swan AV, Willison HJ, Winer JB, Hughes RA . 34461129 . 6 . A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barré syndrome . en . Neurology . 61 . 9 . 1282–4 . November 2003 . 14610140 . 10.1212/01.WNL.0000092019.53628.88 .
18. Pozzilli C, Bastianello S, Koudriavtseva T, Gasperini C, Bozzao A, Millefiorini E, Galgani S, Buttinelli C, Perciaccante G, Piazza G, Bozzao L, Fieschi C . 6 . Magnetic resonance imaging changes with recombinant human interferon-beta-1a: a short term study in relapsing-remitting multiple sclerosis . en . Journal of Neurology, Neurosurgery, and Psychiatry . 61 . 3 . 251–8 . September 1996 . 8795595 . 10.1136/jnnp.61.3.251 . 486547 .
19. Bayne ML, Applebaum J, Chicchi GG, Hayes NS, Green BG, Cascieri MA . Expression, purification and characterization of recombinant human insulin-like growth factor I in yeast . en . Gene . 66 . 2 . 235–44 . June 1988 . 3049246 . 10.1016/0378-1119(88)90360-5 .
20. Jeha S, Kantarjian H, Irwin D, Shen V, Shenoy S, Blaney S, Camitta B, Pui CH . 6 . Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial . en . Leukemia . 19 . 1 . 34–8 . January 2005 . 15510203 . 10.1038/sj.leu.2403566 . 13359871 .
21. Juturu V, Wu JC . Microbial xylanases: engineering, production and industrial applications . en . Biotechnology Advances . 30 . 6 . 1219–27 . 2012 . 22138412 . 10.1016/j.biotechadv.2011.11.006 .
22. Sumantha A, Larroche C, Pandey A . Food Technology and Biotechnology . Microbiology and Industrial Biotechnology of Food-Grade Proteases: A Perspective. . 44 . 211–220 . 2006 . en .
23. Maurer KH . Detergent proteases . en . Current Opinion in Biotechnology . 15 . 4 . 330–4 . August 2004 . 15296930 . 10.1016/j.copbio.2004.06.005 .
24. Li Y, McLarin MA, Middleditch MJ, Morrow SJ, Kilmartin PA, Leung IK . An approach to recombinantly produce mature grape polyphenol oxidase . en . Biochimie . 165 . 40–47 . October 2019 . 31283975 . 10.1016/j.biochi.2019.07.002 . 195843308 .
25. Derardja AE, Pretzler M, Kampatsikas I, Barkat M, Rompel A . Purification and Characterization of Latent Polyphenol Oxidase from Apricot (Prunus armeniaca L.) . en . Journal of Agricultural and Food Chemistry . 65 . 37 . 8203–8212 . September 2017 . 28812349 . 10.1021/acs.jafc.7b03210 . 5609118 .
26. Katayama-Ikegami A, Suehiro Y, Katayama T, Jindo K, Itamura H, Esumi T . Recombinant expression, purification, and characterization of polyphenol oxidase 2 (VvPPO2) from "Shine Muscat" (Vitis labruscana Bailey × Vitis vinifera L.) . en . Bioscience, Biotechnology, and Biochemistry . 81 . 12 . 2330–2338 . December 2017 . 29017399 . 10.1080/09168451.2017.1381017 . free .
27. Marková E, Kotik M, Křenková A, Man P, Haudecoeur R, Boumendjel A, Hardré R, Mekmouche Y, Courvoisier-Dezord E, Réglier M, Martínková L . 6 . Recombinant Tyrosinase from Polyporus arcularius: Overproduction in Escherichia coli, Characterization, and Use in a Study of Aurones as Tyrosinase Effectors . en . Journal of Agricultural and Food Chemistry . 64 . 14 . 2925–31 . April 2016 . 26961852 . 10.1021/acs.jafc.6b00286 .
28. Dirks-Hofmeister ME, Kolkenbrock S, Moerschbacher BM . Parameters that enhance the bacterial expression of active plant polyphenol oxidases . en . PLOS ONE . 8 . 10 . e77291 . 2013 . 24204791 . 10.1371/journal.pone.0077291 . 3804589 . 2013PLoSO...877291D . free .
29. Kampatsikas I, Bijelic A, Pretzler M, Rompel A . Three recombinantly expressed apple tyrosinases suggest the amino acids responsible for mono- versus diphenolase activity in plant polyphenol oxidases . Scientific Reports . 7 . 1 . 8860 . August 2017 . 28821733 . 5562730 . 10.1038/s41598-017-08097-5 . 2017NatSR...7.8860K .
30. Ba S, Vinoth Kumar V . 24681877 . Recent developments in the use of tyrosinase and laccase in environmental applications . en . Critical Reviews in Biotechnology . 37 . 7 . 819–832 . November 2017 . 28330374 . 10.1080/07388551.2016.1261081 .
31. Tremblay J, Goulet MC, Michaud D . Recombinant cystatins in plants . en . Biochimie . 166 . 184–193 . November 2019 . 31194996 . 10.1016/j.biochi.2019.06.006 . 189813855 .
32. Kondo H, Abe K, Nishimura I, Watanabe H, Emori Y, Arai S . Two distinct cystatin species in rice seeds with different specificities against cysteine proteinases. Molecular cloning, expression, and biochemical studies on oryzacystatin-II . en . The Journal of Biological Chemistry . 265 . 26 . 15832–7 . September 1990 . 10.1016/S0021-9258(18)55473-9 . 1697595 . free .
33. Abe K, Kondo H, Arai S . Agricultural and Biological Chemistry . Purification and Characterization of a Rice Cysteine Proteinase Inhibitor. . 51 . 2763–2768 . 1987 . 10 . en . 10.1080/00021369.1987.10868462 .
34. Abe K, Emori Y, Kondo H, Suzuki K, Arai S . Molecular cloning of a cysteine proteinase inhibitor of rice (oryzacystatin). Homology with animal cystatins and transient expression in the ripening process of rice seeds . en . The Journal of Biological Chemistry . 262 . 35 . 16793–7 . December 1987 . 10.1016/S0021-9258(18)45453-1 . 3500172 . free .
35. Kunert KJ, van Wyk SG, Cullis CA, Vorster BJ, Foyer CH . Potential use of phytocystatins in crop improvement, with a particular focus on legumes . en . Journal of Experimental Botany . 66 . 12 . 3559–70 . June 2015 . 25944929 . 10.1093/jxb/erv211 . free . 2263/49447 . free .
36. Mate DM, Alcalde M . Laccase: a multi-purpose biocatalyst at the forefront of biotechnology . en . Microbial Biotechnology . 10 . 6 . 1457–1467 . November 2017 . 27696775 . 5658592 . 10.1111/1751-7915.12422 .
37. Tonin F, Rosini E, Piubelli L, Sanchez-Amat A, Pollegioni L . Different recombinant forms of polyphenol oxidase A, a laccase from Marinomonas mediterranea . en . Protein Expression and Purification . 123 . 60–9 . July 2016 . 27050199 . 10.1016/j.pep.2016.03.011 .
38. Osma JF, Toca-Herrera JL, Rodríguez-Couto S . Uses of laccases in the food industry . en . Enzyme Research . 2010 . 918761 . September 2010 . 21048873 . 2963825 . 10.4061/2010/918761 . free .
39. Minussi RC, Pastore GM, Durán N . Trends Food Sci. Technol. . Potential applications of laccase in the food industry. . 13 . 205–216 . 2002 . 6–7 . en . 10.1016/S0924-2244(02)00155-3 .
40. Horsch J, Wilke P, Pretzler M, Seuss M, Melnyk I, Remmler D, Fery A, Rompel A, Börner HG . 6 . Polymerizing Like Mussels Do: Toward Synthetic Mussel Foot Proteins and Resistant Glues . Angewandte Chemie . 57 . 48 . 15728–15732 . November 2018 . 30246912 . 6282983 . 10.1002/anie.201809587 .