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Cloning, soluble expression and purification of high yield recombinant hGMCSF in Escherichia coli

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논문

Cloning, soluble expression and purification of high yield recombinant hGMCSF in Escherichia coli

학술지

International journal of molecular sciences

저자명

Das, Krishna M.P.; Banerjee, Sampali; Shekhar, Nivedita; Damodaran, Karpagavalli; Nair, Rahul; Somani, Sandeep; Raiker, Veena P.; Jain, Shweta; Padmanabhan, Sriram

초록

<P>Expression of human granulocyte macrophage colony stimulating factor (hGMCSF), a cytokine of therapeutic importance, as a thioredoxin (TRX) fusion has been investigated in <I>Escherichia coli</I> BL21 (DE3) codon plus cells. The expression of this protein was low when cloned under the T7 promoter without any fusion tags. High yield of GMCSF was achieved (∼88 mg/L of fermentation broth) in the shake flask when the gene was fused to the <I>E. coli</I> TRX gene. The protein was purified using a single step Ni<SUP>2+</SUP>-NTA affinity chromatography and the column bound fusion tag was removed by on-column cleavage with enterokinase. The recombinant hGMCSF was expressed as a soluble and biologically active protein in <I>E. coli</I>, and upon purification, the final yield was ∼44 mg/L in shake flask with a specific activity of 2.3 × 10<SUP>8</SUP> U/mg. The results of Western blot and RP-HPLC analyses, along with biological activity using the TF-1 cell line, established the identity of the purified hGMCSF. In this paper, we report the highest yield of hGMCSF expressed in <I>E. coli</I>. The bioreactor study shows that the yield of hGMCSF could be easily scalable with a yield of ∼400 mg/L, opening up new opportunities for large scale production hGMCSF in <I>E. coli</I>.</P>

발행연도

2011

발행기관

Molecular Diversity Preservation International (MDPI)

라이선스

cc-by

ISSN

1661-6596

ISSN

1422-0067

12

3

페이지

pp.2064-2076

주제어

human granulocyte macrophage colony stimulating factor; on-column cleavage; TRX fusion; IMAC; enterokinase

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논문; 2011-03-22

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