Browse > Article
http://dx.doi.org/10.4014/jmb.1511.11010

High-Level Production of Human Papillomavirus (HPV) Type 16 L1 in Escherichia coli  

Bang, Hyun Bae (Department of Chemical and Biomolecular Engineering (BK21 Plus Program), KAIST)
Lee, Yoon Hyeok (Department of Chemical and Biomolecular Engineering (BK21 Plus Program), KAIST)
Lee, Yong Jae (Department of Chemical and Biomolecular Engineering (BK21 Plus Program), KAIST)
Jeong, Ki Jun (Department of Chemical and Biomolecular Engineering (BK21 Plus Program), KAIST)
Publication Information
Journal of Microbiology and Biotechnology / v.26, no.2, 2016 , pp. 356-363 More about this Journal
Abstract
Human papillomavirus (HPV), a non-enveloped, double-stranded DNA tumor virus, is a primary etiological agent of cervical cancer development. As a potential tool for prophylactic vaccination, the development of virus-like particles (VLPs) containing the HPV16 L1 capsid protein is highly desired. In this study, we developed a high-level expression system of the HPV16 L1 in Escherichia coli for the purpose of VLP development. The native gene of HPV16 L1 has many rare codons that cause the early termination of translation and result in the production of truncated forms. First, we optimized the codon of the HPV16 L1 gene to the preferable codons of E. coli, and we succeeded in producing the full-size HPV16 L1 protein without early termination. Next, to find the best host for the production of HPV16 L1, we examined a total of eight E. coli strains, and E. coli BL21(DE3) with the highest yield among the strains was selected. With the selected host-vector system, we did a fed-batch cultivation in a lab-scale bioreactor. Two different feeding solutions (complex and defined feeding solutions) were examined and, when the complex feeding solution was used, a 6-fold higher production yield (4.6 g/l) was obtained compared with that with the defined feeding solution.
Keywords
Human papillomavirus; Escherichia coli; codon optimization; fed-batch cultivation;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Abdoli A, Soleimanjahi H, Fotouhi F, Teimoori A, Pour Beiranvand S, Kianmehr Z. 2013. Human papillomavirus type16-L1 VLP production in insect cells. Iran. J. Basic Med. Sci. 16: 891-895.
2 Bolhassani A, Shirbaghaee Z, Agi E, Davoudi N. 2015. VLP production in Leishmania tarentolae: a novel expression system for purification and assembly of HPV16 L1. Protein Expr. Purif. DOI: 10.1016/j.pep.2015.08.024.   DOI
3 Baek JO, Seo JW, Kwon O, Park SM, Kim CH, Kim IH. 2012. Production of human papillomavirus type 33 L1 major capsid protein and virus-like particles from Bacillus subtilis to develop a prophylactic vaccine against cervical cancer. Enzyme Microb. Technol. 50: 173-180.   DOI
4 Bazan SB, de Alencar Muniz Chaves A, Aires KA, Cianciarullo AM, G arcea R L, H o PL. 2009. Expression a nd characterization of HPV-16 L1 capsid protein in Pichia pastoris. Arch. Virol. 154: 1609-1617.   DOI
5 Bishop B, Dasgupta J, Klein M, Garcea RL, Christensen ND, Zhao R, Chen XS. 2007. Crystal structures of four types of human papillomavirus L1 capsid proteins: understanding the specificity of neutralizing monoclonal antibodies. J. Biol. Chem. 282: 31803-31811.   DOI
6 Brotherton JML, Ogilvie GS. 2015. Current status of human papillomavirus vaccination. Curr. Opin. Oncol. 27: 399-404.   DOI
7 Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. 2000. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol. Cell 5: 557-567.   DOI
8 Corisdeo S, Wang B. 2004. Functional expression and display of an antibody Fab fragment in Escherichia coli: study of vector designs and culture conditions. Protein Expr. Purif. 34: 270-279.   DOI
9 Ermolaeva MD. 2001 Synonymous codon usage in bacteria. Curr. Issues Mol. Biol. 3: 91-97.
10 Grant SGN, Jessee J, Bloom FR, Hanahan D. 1990. Differential plasmid rescue from transgenic mouse DNAs into Escherichia coli methylation-restriction mutants. Proc. Natl. Acad. Sci. USA 87: 4645-4649.   DOI
11 Jeong KJ, Rani M. 2011. High-level production of a single chain antibody against anthrax toxin in Escherichia coli by high cell density cultivation. Bioprocess Biosyst. Eng. 34: 811-817.   DOI
12 Jung ST, Jeong KJ, Iverson BL, Georgiou G. 2007. Binding and enrichment of Escherichia coli spheroplasts expressing inner membrane tethered scFv antibodies on surface immobilized antigens. Biotechnol. Bioeng. 98: 39-47.   DOI
13 Griswold KE, Kawarasaki Y, Ghoneim N, Benkovic SJ, Iverson BL, Georgiou G. 2005. Evolution of highly active enzymes by homology-independent recombination. Proc. Natl. Acad. Sci. USA 102: 10082-10087.   DOI
14 Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, et al. 2004. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364: 1757-1765.   DOI
15 Jeong KJ, Lee SY. 2003. Enhanced production of recombinant proteins in Escherichia coli by filamentation suppression. Appl. Environ. Microbiol. 69: 1295-1298.   DOI
16 Kane JF. 1995. Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr. Opin. Biotechnol. 6: 494-500.   DOI
17 Kim HJ, Lee SJ, Kim HJ. 2010. Optimizing the secondary structure of human papillomavirus type 16 L1 mRNA enhances L1 protein expression in Saccharomyces cerevisiae. J. Biotechnol. 150: 31-36.   DOI
18 Lee SY. 1996. High cell-density culture of Escherichia coli. Trends Biotechnol. 14: 98-105.   DOI
19 Lee YJ, Lee DH, Jeong KJ. 2014. Enhanced production of human full-length immunoglobulin G1 in the periplasm of Escherichia coli. Appl. Microbiol. Biotechnol. 98: 1237-1246.   DOI
20 Schadlich L, Senger T, Kirschning CJ, Muller M, Gissmann L. 2009 Refining HPV 16 L1 purification from E. coli: reducing endotoxin contaminations and their impact on immunogenicity. Vaccine 27: 1511-1522.   DOI
21 Schiller JT, Lowy DR. 1996. Papillomavirus-like particles and HPV vaccine development. Semin. Cancer Biol. 7: 373-382.   DOI
22 Pineo CB, Hitzeroth II, Rybicki EP. 2013. Immunogenic assessment of plant-produced human papillomavirus type 16 L1/L2 chimaeras. Plant Biotechnol. J. 11: 964-975.   DOI
23 Sambrook J, Russell D. 2001. Molecular cloning: a laboratory manual. Q. Rev. Biol. 76: 348-349.
24 Sapp M, Volpers C, Muller M, Streeck RE. 1995. Organization of the major and minor capsid proteins in human papillomavirus type 33 virus-like particles. J. Gen. Virol. 76: 2407-2412.   DOI
25 Seo PS, Heo SY, Han EJ, Seo JW, Ghim SJ, Kim CH. 2009. Bacterial expression and purification of human papillomavirus type 18 L1. Biotechnol. Bioprocess Eng. 14: 168-174.   DOI
26 Sorensen MA, Kurland CG, Pedersen S. 1989. Codon usage determines translation rate in Escherichia coli. J. Mol. Biol. 207: 365-377.   DOI
27 Villa LL, Costa RLR, Petta CA, Andrade RP, Paavonen J, Iversen OE, et al. 2006. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br. J. Cancer 95: 1459-1466.   DOI
28 Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 189: 12-19.   DOI
29 Zheng DD, Pan D, Zha X, Wu Y, Jiang C, Yu X. 2013. In vitro monitoring of the formation of pentamers from the monomer of GST fused HPV 16 L1. Chem. Commun. 49: 8546-8548.   DOI
30 Yanisch-Perron C, Vieira J, Messing J. 1985. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene 33: 103-119.   DOI
31 Yim SC, Jeong KJ, Chang HN, Lee SY. 2001. High-level secretory production of human granulocyte-colony stimulating factor by fed-batch culture of recombinant Escherichia coli. Bioprocess Biosyst. Eng. 24: 249-254.   DOI
32 Yun HS, Park JJ, Choi IK, Kee MK, Choi BS, Kim SS. 2008. Prevalence of human papillomavirus and herpes simplex virus type 2 infection in Korean commercial sex workers. J. Microbiol. Biotechnol. 18: 350-354.