Transplastomic biofactory for the production of functional human α-lactalbumin for nutritional and therapeutic applications

transplastomic-biofactory-for-the-production-of-functional-human-α-lactalbumin-for-nutritional-and-therapeutic-applications
Transplastomic biofactory for the production of functional human α-lactalbumin for nutritional and therapeutic applications

References

  1. Smith, N. W., Fletcher, A. J., Hill, J. P. & McNabb, W. C. Modeling the contribution of milk to global nutrition. Front. Nutr. 8, 716100 (2022).

    Google Scholar 

  2. Behm, K. et al. Comparison of carbon footprint and water scarcity footprint of milk protein produced by cellular agriculture and the dairy industry. Int. J. Life Cycle Assess. 27 (8), 1017–1034 (2022).

    Google Scholar 

  3. Andreas, N. J., Kampmann, B. & Le-Doare, K. M. Human breast milk: A review on its composition and bioactivity. Early Hum. Dev. 91 (11), 629–635 (2015).

    Google Scholar 

  4. Heine, W. E., Klein, P. D. & Reeds, P. J. The importance of α-lactalbumin in infant nutrition. J. Nutr. 121 (3), 277–283 (1991).

    Google Scholar 

  5. Permyakov, E. A. α-Lactalbumin, amazing calcium-binding protein. Biomolecules 10 (9), 1210 (2020).

    Google Scholar 

  6. Giuffrida, M. G. et al. The unusual amino acid triplet Asn-Ile-Cys is a glycosylation consensus site in human alpha-lactalbumin. J. Protein Chem. 16 (8), 747–753. https://doi.org/10.1023/a:1026359715821 (1997).

    Google Scholar 

  7. Kunz, C. & Lönnerdal, B. Re-evaluation of the Whey protein/casein ratio of human milk. Acta Paediatr. 81 (2), 107–112 (1992).

    Google Scholar 

  8. Layman, D. K., Lönnerdal, B. & Fernstrom, J. D. Applications for α-lactalbumin in human nutrition. Nutr. Rev. 76 (6), 444–460 (2018).

    Google Scholar 

  9. Enomoto, H. et al. Glycation and phosphorylation of α-lactalbumin by dry heating: effect on protein structure and physiological functions. J. Dairy Sci. 92 (7), 3057–3068 (2009).

    Google Scholar 

  10. Lien, E. L. Infant formulas with increased concentrations of α-lactalbumin. Am. J. Clin. Nutr. 77 (6), 1555S–1558S (2003).

    Google Scholar 

  11. Lönnerdal, B. Infant formula and infant nutrition: bioactive proteins of human milk and implications for composition of infant formulas. Am. J. Clin. Nutr. 99 (3), 712S–717S (2014).

    Google Scholar 

  12. Mossberg, A. K., Mok, H., Morozova-Roche, K., Svanborg, C. & L. A., & Structure and function of human α‐lactalbumin made lethal to tumor cells (HAMLET)‐type complexes. FEBS J. 277 (22), 4614–4625 (2010).

    Google Scholar 

  13. Permyakov, E. A. & Berliner, L. J. α-Lactalbumin: structure and function. FEBS Lett. 473 (3), 269–274 (2000).

    Google Scholar 

  14. Hettinga, K. & Bijl, E. Can Recombinant milk proteins replace those produced by animals? Curr. Opin. Biotechnol. 75, 102690 (2022).

    Google Scholar 

  15. Awasthi, V. et al. Contaminants in milk and impact of heating: an assessment study. Indian J. Public Health. 56 (1), 95–99 (2012).

    Google Scholar 

  16. Geistlinger, T. et al. Recombinant components and compositions for use in food products. Google Patents (2022).

  17. Vestergaard, M., Chan, S. H. J. & Jensen, P. R. Can microbes compete with cows for sustainable protein production-A feasibility study on high quality protein. Sci. Rep. 6 (1), 36421 (2016).

    Google Scholar 

  18. Chaudhuri, T. K. et al. Effect of the extra N-terminal methionine residue on the stability and folding of Recombinant α-lactalbumin expressed in Escherichia coli. J. Mol. Biol. 285 (3), 1179–1194 (1999).

    Google Scholar 

  19. Overton, T. W. Recombinant protein production in bacterial hosts. Drug Discovery Today. 19 (5), 590–601 (2014).

    Google Scholar 

  20. Deng, M. et al. Efficient bioproduction of human milk Alpha-Lactalbumin in Komagataella phaffii. J. Agric. Food Chem. 70 (8), 2664–2672 (2022).

    Google Scholar 

  21. Saito, A., Usui, M., Song, Y., Azakami, H. & Kato, A. Secretion of glycosylated α-lactalbumin in yeast Pichia pastoris. J. Biochem. 132 (1), 77–82 (2002).

    Google Scholar 

  22. Demain, A. L. & Vaishnav, P. Production of Recombinant proteins by microbes and higher organisms. Biotechnol. Adv. 27 (3), 297–306 (2009).

    Google Scholar 

  23. Long, C. Transgenic livestock for agriculture and biomedical applications. In BMC Proceedings 8 (4), O29. https://doi.org/10.1186/1753-6561-8-S4-O29 (BioMed Central, 2014).

  24. Bicar, E. H. et al. Transgenic maize endosperm containing a milk protein has improved amino acid balance. Transgenic Res. 17, 59–71 (2008).

    Google Scholar 

  25. Salmon, V. et al. Production of human lactoferrin in Transgenic tobacco plants. Protein Exp. Purif. 13 (1), 127–135 (1998).

    Google Scholar 

  26. Bock, R. Structure, function, and inheritance of plastid genomes. In Cell and Molecular Biology of Plastids 29–63. (Springer, 2007).

  27. Chebolu, S. & Daniell, H. Chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding, assembly and functionality. Plant Produced Microb. Vaccines 33–54. (2009).

  28. Koop, H. U., Herz, S., Golds, T. J. & Nickelsen, J. The genetic transformation of plastids. Cell Mol. Biol. Plastids 457–510. (2007).

  29. Maliga, P. Engineering the plastid genome of higher plants. Curr. Opin. Plant. Biol. 5 (2), 164–172 (2002).

    Google Scholar 

  30. Oey, M., Lohse, M., Kreikemeyer, B. & Bock, R. Exhaustion of the Chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J. 57 (3), 436–445 (2009).

    Google Scholar 

  31. Oey, M., Lohse, M., Scharff, L. B., Kreikemeyer, B. & Bock, R. Plastid production of protein antibiotics against pneumonia via a new strategy for high-level expression of antimicrobial proteins. Proc. Natl. Acad. Sci. 106 (16), 6579–6584. (2009).

  32. Daniell, H., Streatfield, S. J. & Wycoff, K. Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci. 6 (5), 219–226 (2001).

    Google Scholar 

  33. Fischer, R., Stoger, E., Schillberg, S., Christou, P. & Twyman, R. M. Plant-based production of biopharmaceuticals. Curr. Opin. Plant. Biol. 7 (2), 152–158 (2004).

    Google Scholar 

  34. Ma, J. K. C. et al. Molecular farming for new drugs and vaccines: current perspectives on the production of pharmaceuticals in Transgenic plants. EMBO Rep. 6 (7), 593–599 (2005).

    Google Scholar 

  35. Ehsasatvatan, M., Kohnehrouz, B. B., Gholizadeh, A., Ofoghi, H. & Shanehbandi, D. The production of the first functional antibody mimetic in higher plants: the Chloroplast makes the DARPin G3 for HER2 imaging in oncology. Biol. Res. 55 (1), 1–18 (2022b).

    Google Scholar 

  36. Zoubenko, O. V., Allison, L. A., Svab, Z. & Maliga, P. Efficient targeting of foreign genes into the tobacco plastid genome. Nucleic Acids Res. 22 (19), 3819–3824 (1994).

    Google Scholar 

  37. Ehsasatvatan, M., Kohnehrouz, B. B., Gholizadeh, A., Ofoghi, H. & Shanehbandi, D. Physical and biologically effective parameters in developing transplastomic tobacco plants by particle bombardment method using PDS-1000/He. Optimization 10 (2). (2022).

  38. Murray, M. & Thompson, W. Rapid isolation of high molecular weight plant DNA. Nucleic Acids Res. 8 (19), 4321–4326 (1980).

    Google Scholar 

  39. Kamijima, T. et al. Heat-treatment method for producing fatty acid-bound alpha-lactalbumin that induces tumor cell death. Biochem. Biophys. Res. Commun. 376 (1), 211–214 (2008).

    Google Scholar 

  40. Žilinskas, J. et al. HAMLET effect on cell death and mitochondrial respiration in colorectal cancer cell lines with KRAS/BRAF mutations. J. Cancer Res. Clin. Oncol. 149 (11), 8619–8630 (2023).

    Google Scholar 

  41. Miller, E. Apoptosis measurement by Annexin V staining. Cancer Cell. Culture Methods Protoc. 191–202. (2004).

  42. Jensen, R. G. Activation of Rubisco regulates photosynthesis at high temperature and CO2. Proc. Natl. Acad. Sci. 97 (24), 12937–12938. (2000).

  43. Krishnan, H. B. & Natarajan, S. S. A rapid method for depletion of Rubisco from soybean (Glycine max) leaf for proteomic analysis of lower abundance proteins. Phytochemistry 70 (17–18), 1958–1964 (2009).

    Google Scholar 

  44. Ramboarina, S. & Redfield, C. Structural characterisation of the human alpha-lactalbumin molten globule at high temperature. J. Mol. Biol. 330 (5), 1177–1188. https://doi.org/10.1016/s0022-2836(03)00639-9 (2003).

    Google Scholar 

  45. Piazenski, I. N. et al. From lab to table: the path of recombinant milk proteins in transforming dairy production. Trends Food Sci. Technol. 104562. (2024).

  46. Batt, C. A., Rabson, L. D., Wong, D. W. & Kinsella, J. E. Expression of Recombinant bovine β-lactoglobulin in Escherichia coli. Agric. Biol. Chem. 54 (4), 949–955 (1990).

    Google Scholar 

  47. Goda, S. et al. Recombinant expression analysis of natural and synthetic bovine alpha-casein in Escherichia coli. Appl. Microbiol. Biotechnol. 54, 671–676 (2000).

    Google Scholar 

  48. Kim, Y. et al. High-level expression of human α s1-casein in Escherichia coli. Biotechnol. Tech. 11, 675–678 (1997).

    Google Scholar 

  49. Kalidas, C., Joshi, L. & Batt, C. Characterization of glycosylated variants of β-lactoglobulin expressed in Pichia pastoris. Protein Eng. 14 (3), 201–207 (2001).

    Google Scholar 

  50. Kim, Y. K., Yu, D. Y., Kang, H. A., Yoon, S. & Chung, B. H. Secretory expression of human $alpha_ {s1} $-Casein in Saccharomyces cerevisiae. J. Microbiol. Biotechnol. 9 (2), 196–200 (1999).

    Google Scholar 

  51. Totsuka, M. et al. Expression and secretion of bovine β-lactoglobulin in Saccharomyces cerevisiae. Agric. Biol. Chem. 54 (12), 3111–3116 (1990).

    Google Scholar 

  52. Sun, X. L., Baker, H. M., Shewry, S. C., Jameson, G. B. & Baker, E. N. Structure of Recombinant human lactoferrin expressed in Aspergillus Awamori. Acta Crystallogr., Sect D: Biol. Crystallogr. 55 (2), 403–407 (1999).

    Google Scholar 

  53. Chong, D. et al. Expression of the human milk protein β-casein in Transgenic potato plants. Transgenic Res. 6, 289–296 (1997).

    Google Scholar 

  54. Huang, N., Rodriguez, R. L. & Hagie, F. E. Expression of human milk proteins in transgenic plants. Google Patents (2014).

  55. Lanquar, V. & Magi, E. R. Recombinant milk proteins and food compositions comprising the same. Google Patents (2022).

  56. Tobin, C. J. Recombinant micelle and method of in vivo assembly. Google Patents (2022).

  57. Ehsasatvatan, M. & Kohnehrouz, B. B. The lyophilized chloroplasts store synthetic DARPin G3 as bioactive encapsulated organelles. J. Biol. Eng. 17 (1), 63 (2023).

    Google Scholar 

  58. Scotti, N., Bellucci, M. & Cardi, T. The chloroplasts as platform for Recombinant proteins production. In Translation in Mitochondria and Other Organelles 225–262. (Springer, 2013).

  59. Boyhan, D. & Daniell, H. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C‐peptide. Plant Biotechnol. J. 9 (5), 585–598 (2011).

    Google Scholar 

  60. Hakansson, A., Zhivotovsky, B., Orrenius, S., Sabharwal, H. & Svanborg, C. Apoptosis induced by a human milk protein. Proc. Natl. Acad. Sci. 92 (17), 8064–8068 (1995).

    Google Scholar 

  61. Ho Cs, J., Rydstrom, A., Manimekalai, M. S. S., Svanborg, C. & Grüber, G. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity. PloS ONE 7 (12), e53051. (2012).

  62. Svensson, M. et al. Molecular characterization of α–lactalbumin folding variants that induce apoptosis in tumor cells. J. Biol. Chem. 274 (10), 6388–6396 (1999).

    Google Scholar 

Download references