Microbial factories for recombinant pharmaceuticals

被引:299
作者
Ferrer-Miralles, Neus [1 ,2 ,3 ]
Domingo-Espin, Joan [1 ,2 ,3 ]
Corchero, Jose Luis [1 ,3 ]
Vazquez, Esther [1 ,2 ,3 ]
Villaverde, Antonio [1 ,2 ,3 ]
机构
[1] Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
[2] Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
[3] CIBER BBN, Barcelona, Spain
关键词
PROTEIN-PRODUCTION; ESCHERICHIA-COLI; PICHIA-PASTORIS; THERAPEUTIC PROTEINS; FILAMENTOUS FUNGI; INSECT CELLS; SIALIC-ACID; EXPRESSION; STRATEGIES; YEASTS;
D O I
10.1186/1475-2859-8-17
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way.
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页数:8
相关论文
共 54 条
[1]  
[Anonymous], 1982, FDA Drug Bull, V12, P18
[2]   A transgenic insect cell line engineered to produce CMP-sialic acid and sialylated glycoproteins [J].
Aumiller, JJ ;
Hollister, JR ;
Jarvis, DL .
GLYCOBIOLOGY, 2003, 13 (06) :497-507
[3]  
Bailon P, 2009, EXPERT OPIN DRUG DEL, V6, P1, DOI [10.1517/17425240802650568 , 10.1517/17425240802650568]
[4]  
Bleckwenn NA., 2004, Curr Protoc Immunol, pA.1U.1
[5]   Metabolically engineered yeasts: 'Potential' industrial applications [J].
Branduardi, Paola ;
Smeraldi, Carla ;
Porro, Danilo .
JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 2008, 15 (01) :31-40
[6]   A novel genetic system for recombinant protein secretion in the Antarctic Pseudoalteromonas haloplanktis TAC125 [J].
Cusano, Angela Maria ;
Parrilli, Ermenegilda ;
Marino, Gennaro ;
Tutino, Maria Luisa .
MICROBIAL CELL FACTORIES, 2006, 5 (1)
[7]   Protocol for preparing proteins with improved solubility by co-expressing with molecular chaperones in Escherichia coli [J].
de Marco, Ario .
NATURE PROTOCOLS, 2007, 2 (10) :2632-2639
[8]   Minimal information: an urgent need to assess the functional reliability of recombinant proteins used in biological experiments [J].
de Marco, Ario .
MICROBIAL CELL FACTORIES, 2008, 7 (1)
[9]   Aggregation as bacterial inclusion bodies does not imply inactivation of enzymes and fluorescent proteins -: art. no. 27 [J].
García-Fruitós, E ;
González-Montalbán, N ;
Morell, M ;
Vera, A ;
Ferraz, RM ;
Arís, A ;
Ventura, S ;
Villaverde, A .
MICROBIAL CELL FACTORIES, 2005, 4 (1)
[10]   Localization of functional polypeptides in bacterial inclusion bodies [J].
Garcia-Fruitos, Elena ;
Aris, Anna ;
Villaverde, Antonio .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2007, 73 (01) :289-294