Gene switch for l-glucose-induced biopharmaceutical production in mammalian cells.
LgdA
LgnH
LgnI
LgnR
SMIT1
d-idonate
l-glucose
synthetic biology
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
23
01
2021
received:
18
11
2020
accepted:
17
02
2021
pubmed:
26
2
2021
medline:
14
1
2022
entrez:
25
2
2021
Statut:
ppublish
Résumé
In this study, we designed and built a gene switch that employs metabolically inert l-glucose to regulate transgene expression in mammalian cells via d-idonate-mediated control of the bacterial regulator LgnR. To this end, we engineered a metabolic cascade in mammalian cells to produce the inducer molecule d-idonate from its precursor l-glucose by ectopically expressing the Paracoccus species 43P-derived catabolic enzymes LgdA, LgnH, and LgnI. To obtain ON- and OFF-switches, we fused LgnR to the human transcriptional silencer domain Krüppel associated box (KRAB) and the viral trans-activator domain VP16, respectively. Thus, these artificial transcription factors KRAB-LgnR or VP16-LgnR modulated cognate promoters containing LgnR-specific binding sites in a d-idonate-dependent manner as a direct result of l-glucose metabolism. In a proof-of-concept experiment, we show that the switches can control production of the model biopharmaceutical rituximab in both transiently and stably transfected HEK-293T cells, as well as CHO-K1 cells. Rituximab production reached 5.9 µg/ml in stably transfected HEK-293T cells and 3.3 µg/ml in stably transfected CHO-K1 cells.
Substances chimiques
Sugar Acids
0
Transcription Factors
0
idonic acid
1114-17-6
Rituximab
4F4X42SYQ6
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2220-2233Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Ahler, E., Sullivan, W. J., Cass, A., Braas, D., York, A. G., Bensinger, S. J., & Christofk, H. R. (2013). Doxycycline alters metabolism and proliferation of human cell lines. PLOS One, 8(5), e64561. https://doi.org/10.1371/journal.pone.0064561
Amann, T., Schmieder, V., Faustrup Kildegaard, H., Borth, N., & Andersen, M. R. (2019). Genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms. Biotechnology and Bioengineering, 116(10), 2778-2796. https://doi.org/10.1002/bit.27101
Bebbington, C. R., Renner, G., Thomson, S., King, D., Abrams, D., & Yarranton, G. T. (1992). High-level expression of a recombinant antibody from myeloma cells using a glutamine-synthetase gene as an amplifiable selectable marker. Bio-Technology, 10(2), 169-175. https://doi.org/10.1038/nbt0292-169
Belliveau, P. P. (2005). Omalizumab: A monoclonal anti-IgE antibody. MedGenMed, 7(1), 27.
Berger, J., Hauber, J., Hauber, R., Geiger, R., & Cullen, B. R. (1988). Secreted placental alkaline phosphatase: A powerful new quantitative indicator of gene expression in eukaryotic cells. Gene, 66(1), 1-10. https://doi.org/10.1016/0378-1119(88)90219-3
Brady, R. O., Pentchev, P. G., Gal, A. E., Hibbert, S. R., & Dekaban, A. S. (1974). Replacement therapy for inherited enzyme deficiency-Use of purified glucocerebrosidase in gauchers-disease. New England Journal of Medicine, 291(19), 989-993. https://doi.org/10.1056/Nejm197411072911901
Brady, R. O., Tallman, J. F., Johnson, W. G., Gal, A. E., Leahy, W. R., Quirk, J. M., & Dekaban, A. S. (1973). Replacement therapy for inherited enzyme deficiency-Use of purified ceramidetrihexosidase in fabrys-disease. New England Journal of Medicine, 289(1), 9-14. https://doi.org/10.1056/Nejm197307052890103
Brown, M. E., Renner, G., Field, R. P., & Hassell, T. (1992). Process-development for the production of recombinant antibodies using the glutamine-synthetase (Gs) system. Cytotechnology, 9(1-3), 231-236. https://doi.org/10.1007/Bf02521750
Chudasama, V., Maruani, A., & Caddick, S. (2016). Corrigendum: Recent advances in the construction of antibody-drug conjugates. Nature Chemistry, 8(3), 281. https://doi.org/10.1038/nchem.2467
Deshaies, R. J. (2020). Multispecific drugs herald a new era of biopharmaceutical innovation. Nature, 580(7803), 329-338. https://doi.org/10.1038/s41586-020-2168-1
Dumont, J., Euwart, D., Mei, B., Estes, S., & Kshirsagar, R. (2016). Human cell lines for biopharmaceutical manufacturing: History, status, and future perspectives. Critical Reviews in Biotechnology, 36(6), 1110-1122. https://doi.org/10.3109/07388551.2015.1084266
Falck, D., Jansen, B. C., de Haan, N., & Wuhrer, M. (2017). High-throughput analysis of IgG Fc glycopeptides by LC-MS. Methods in Molecular Biology, 1503, 31-47. https://doi.org/10.1007/978-1-4939-6493-2_4
Fan, L. C., Kadura, I., Krebs, L. E., Hatfield, C. C., Shaw, M. M., & Frye, C. C. (2012). Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells. Biotechnology and Bioengineering, 109(4), 1007-1015. https://doi.org/10.1002/bit.24365
Fang, J. M., Yi, S. L., Simmons, A., Tu, G. H., Nguyen, M., Harding, T. C., & Jooss, K. (2007). An antibody delivery system for regulated expression of therapeutic levels of monoclonal antibodies in vivo. Molecular Therapy, 15(6), 1153-1159. https://doi.org/10.1038/sj.mt.6300142
Frei, T., Cella, F., Tedeschi, F., Gutierrez, J., Stan, G. B., Khammash, M., & Siciliano, V. (2020). Characterization and mitigation of gene expression burden in mammalian cells. Nature Communications, 11(1), 4641. https://doi.org/10.1038/s41467-020-18392-x
Grabowski, G. A., Leslie, N., & Wenstrup, R. (1998). Enzyme therapy for Gaucher disease: The first 5 years. Blood Reviews, 12(2), 115-133. https://doi.org/10.1016/S0268-960x(98)90023-6
Hager, K., Hazama, A., Kwon, H. M., Loo, D. D., Handler, J. S., & Wright, E. M. (1995). Kinetics and specificity of the renal Na+/myo-inositol cotransporter expressed in Xenopus oocytes. Journal of Membrane Biology, 143(2), 103-113. https://doi.org/10.1007/bf00234656
Hang, I., Lin, C. W., Grant, O. C., Fleurkens, S., Villiger, T. K., Soos, M., & Aebi, M. (2015). Analysis of site-specific N-glycan remodeling in the endoplasmic reticulum and the golgi. Glycobiology, 25(12), 1335-1349. https://doi.org/10.1093/glycob/cwv058
Hansson, K., & Stenflo, J. (2005). Post-translational modifications in proteins involved in blood coagulation. Journal of Thrombosis and Haemostasis, 3(12), 2633-2648. https://doi.org/10.1111/j.1538-7836.2005.01478.x
Huang, M., Bao, J., & Nielsen, J. (2014). Biopharmaceutical protein production by Saccharomyces cerevisiae: Current state and future prospects. Pharmaceutical Bioprocessing, 2(2), 167-182. https://doi.org/10.4155/pbp.14.8
Ioannou, Y. A., Bishop, D. F., & Desnick, R. J. (1992). Overexpression of human alpha-galactosidase-a results in its intracellular aggregation, crystallization in lysosomes, and selective secretion. Journal of Cell Biology, 119(5), 1137-1150. https://doi.org/10.1083/jcb.119.5.1137
Jonker, H. R., Wechselberger, R. W., Boelens, R., Folkers, G. E., & Kaptein, R. (2005). Structural properties of the promiscuous VP16 activation domain. Biochemistry, 44(3), 827-839. https://doi.org/10.1021/bi0482912
Kallunki, T., Barisic, M., Jaattela, M., & Liu, B. (2019). How to choose the right inducible gene expression system for mammalian studies? Cells, 8(8), 796. https://doi.org/10.3390/cells8080796
Kopp, J., Kolkmann, A. M., Veleenturf, P. G., Spadiut, O., Herwig, C., & Slouka, C. (2019). Boosting recombinant inclusion body production-From classical fed-batch approach to continuous cultivation. Frontiers in Bioengineering and Biotechnology, 7, 297. https://doi.org/10.3389/fbioe.2019.00297
Kowarz, E., Loscher, D., & Marschalek, R. (2015). Optimized sleeping beauty transposons rapidly generate stable transgenic cell lines. Biotechnology Journal, 10(4), 647-653. https://doi.org/10.1002/biot.201400821
Levin, G. V., Zehner, L. R., Saunders, J. P., & Beadle, J. R. (1995). Sugar substitutes-Their energy values, bulk characteristics, and potential health benefits. American Journal of Clinical Nutrition, 62(5), 1161-1168.
Lonza. (2019). Lonza chooses synpromics’ novel inducible promoter platform to manufacture biopharmaceuticals. Lonza. May 16. https://pharma.lonza.com/news/2019-05-16-13-00
Magistrelli, G., Poitevin, Y., Schlosser, F., Pontini, G., Malinge, P., Josserand, S., Corbier, M., & Fischer, N. (2017). Optimizing assembly and production of native bispecific antibodies by codon de-optimization. mAbs, 9(2), 231-239. https://doi.org/10.1080/19420862.2016.1267088
Mannully, S. T., L, N. R., & Pulicherla, K. K. (2018). Perspectives on progressive strategies and recent trends in the production of recombinant human factor VIII. International Journal of Biological Macromolecules, 119, 496-504. https://doi.org/10.1016/j.ijbiomac.2018.07.164
Mansouri, M., Strittmatter, T., & Fussenegger, M. (2019). Light-controlled mammalian cells and their therapeutic applications in synthetic biology. Advanced Science, 6(1), 1800952. https://doi.org/10.1002/advs.201800952
Margolin, J. F., Friedman, J. R., Meyer, W. K., Vissing, H., Thiesen, H. J., & Rauscher, F. J., 3rd (1994). Kruppel-associated boxes are potent transcriptional repression domains. Proceedings of the National Academy of Sciences of the United States of America, 91(10), 4509-4513. https://doi.org/10.1073/pnas.91.10.4509
Molina-Henares, A. J., Krell, T., Guazzaroni, M. E., Segura, A., & Ramos, J. L. (2006). Members of the IclR family of bacterial transcriptional regulators function as activators and/or repressors. FEMS Microbiology Reviews, 30(2), 157-186. https://doi.org/10.1111/j.1574-6976.2005.00008.x
Monaco, C., Nanchahal, J., Taylor, P., & Feldmann, M. (2015). Anti-TNF therapy: Past, present and future. International Immunology, 27(1), 55-62. https://doi.org/10.1093/intimm/dxu102
Mufarrege, E. F., Benizio, E. L., Prieto, C. C., Chiappini, F., Rodriguez, M. C., Etcheverrigaray, M., & Kratje, R. B. (2020). Development of Magoh protein-overexpressing HEK cells for optimized therapeutic protein production. Biotechnology and Applied Biochemistry, bab.1915. https://doi.org/10.1002/bab.1915
Muhsin, M., Graham, J., & Kirkpatrick, P. (2004). Bevacizumab. Nature Reviews Drug Discovery, 3(12), 995-996. https://doi.org/10.1038/nrd1601
Pierpont, T. M., Limper, C. B., & Richards, K. L. (2018). Past, present, and future of rituximab-The world's first oncology monoclonal antibody therapy. Frontiers in Oncology, 8, 8. https://doi.org/10.3389/fonc.2018.00163
Reff, M. E., Carner, K., Chambers, K. S., Chinn, P. C., Leonard, J. E., Raab, R., & Anderson, D. R. (1994). Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood, 83(2), 435-445.
Rudney, H. (1940). The utilization of l-glucose by mammalian tissues and bacteria. Science, 92(2379), 112-113. https://doi.org/10.1126/science.92.2379.112
Sasajima, K. I., & Sinskey, A. J. (1979). Oxidation of l-glucose by a Pseudomonad. Biochimica et Biophysica Acta/General Subjects, 571(1), 120-126. https://doi.org/10.1016/0005-2744(79)90232-8
Shimizu, T., & Nakamura, A. (2014). Characterization of LgnR, an IclR family transcriptional regulator involved in the regulation of l-gluconate catabolic genes in Paracoccus sp. 43P. Microbiology, 160(Pt 3), 623-634. https://doi.org/10.1099/mic.0.074286-0
Shimizu, T., Takaya, N., & Nakamura, A. (2012). An l-glucose catabolic pathway in Paracoccus species 43P. Journal of Biological Chemistry, 287(48), 40448-40456. https://doi.org/10.1074/jbc.M112.403055
Stavenhagen, K., Kayili, H. M., Holst, S., Koeleman, C. A. M., Engel, R., Wouters, D., & Wuhrer, M. (2018). N- and O-glycosylation analysis of human C1-inhibitor reveals extensive mucin-type O-Gglycosylation. Molecular & Cellular Proteomics, 17(6), 1225-1238. https://doi.org/10.1074/mcp.RA117.000240
Suh, I. S., & Lee, S. B. (2003). A light distribution model for an internally radiating photobioreactor. Biotechnology and Bioengineering, 82(2), 180-189. https://doi.org/10.1002/bit.10558
Urrutia, R. (2003). KRAB-containing zinc-finger repressor proteins. Genome Biology, 4(10), 231. https://doi.org/10.1186/gb-2003-4-10-231
Yalak, G., & Vogel, V. (2012). Extracellular phosphorylation and phosphorylated proteins: Not just curiosities but physiologically important. Science Signaling, 5(255), re7. https://doi.org/10.1126/scisignal.2003273
Yusa, K., Zhou, L. Q., Li, M. A., Bradley, A., & Craig, N. L. (2011). A hyperactive piggyBac transposase for mammalian applications. Proceedings of the National Academy of Sciences of the United States of America, 108(4), 1531-1536. https://doi.org/10.1073/pnas.1008322108
Zhang, L., Luo, S., & Zhang, B. L. (2016). The use of lectin microarray for assessing glycosylation of therapeutic proteins. mAbs, 8(3), 524-535. https://doi.org/10.1080/19420862.2016.1149662