Title
A new vector for heterologous gene expression in Escherichia coli with increased stability in the absence of antibiotic
Date Issued
01 June 2018
Access level
metadata only access
Resource Type
journal article
Author(s)
Eguia F.
Ramos H.
Kraschowetz S.
Omote D.
Ho P.
Carvalho E.
Gonçalves V.
Instituto Butantan
Publisher(s)
Academic Press Inc.
Abstract
Expression vectors for industrial production should be stable and allow tight control of protein synthesis. This is necessary to ensure plasmid transmission to daughter cells in order to achieve a stable population capable of synthesizing high amounts of the target protein. A high-copy-number plasmid, pAE, was previously used for laboratory-scale production of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the Schistosoma mansoni fatty acid binding protein (rSm14), but it was unstable for large-scale production. Therefore, here we evaluated a new expression vector derived from pAE, pAR-KanI, which combines two plasmid replication strategies: a high-copy plasmid pUC origin of replication as pAE, and a par locus sequence derived from pSC101, which is typical of low copy plasmids, for rhG-CSF and rSm14 production in Escherichia coli. Clones bearing these constructs were cultivated in two complex media (2YT and auto-induction) and both yielded higher-than-95% resistant colonies, before and after induction, either with or without antibiotics. In 2YT medium, we obtained 244 μg/mL of rSm14, 181 μg/mL and 392 μg/mL for rhG-CSF, with and without glucose, respectively. In auto-induction medium without antibiotics, 147 μg/mL of rSm14 and 162 μg/mL of rhG-CSF were obtained. The new vector presented high stability for the production of both recombinant proteins in complex media in Escherichia coli, even in the absence of antibiotics, making the pAR-KanI a promising vector for industrial production of recombinant proteins.
Start page
22
End page
30
Volume
98
Language
English
OCDE Knowledge area
Bioquímica, Biología molecular Biotecnología médica
Scopus EID
2-s2.0-85053150302
PubMed ID
Source
Plasmid
ISSN of the container
0147619X
Sponsor(s)
Fara A. P. Eguia receives a scholarship from CAPES, PEC-PG Program (grant number 12585-13-0 ). Daniel Omote received a scholarship from CNPq, IC Program (grant number 118669/2011-7 ).
Sources of information: Directorio de Producción Científica Scopus