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High-level expression of human cytochrome P450 3A4 by co-expression with Human molecular chaperone HDJ-1 (Hsp40)

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Abstract

Cytochrome P450 (CYP) 3A4 is of great interest because of its important roles in the oxidation of numerous drugs and xenobiotics. HDJ-1, a molecular chaperone in human, is known to assist the correct folding of unfolded proteins. To achieve a high yield of recombinant human CYP3A4 inEscherichia coli, the CYP3A4 encoding gene was co-expressed with the chaperone HDJ-1, under the control of an inducibletac promoter in a bicistronic format. The levels of expression of the CYP3A4 in the bicistronic construct reached up to 715 nmol (liter culture)-1 within 16 h at 37°C, which was about a 3.3-fold increase compared to that of the CYP3A4 alone without the HDJ-1. By co-expression with HDJ-1, the catalytic activity of CYP3A4 was also increased by ~15-fold. The amount of activity increase was similar to that of the CYP production at the whole cell level. The present over-expression system may be useful for the rapid production of large amounts of active CYP3A4 inE. coli.

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Correspondence to Taeho Ahn or Chul-Ho Yun.

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Ahn, T., Yun, CH. High-level expression of human cytochrome P450 3A4 by co-expression with Human molecular chaperone HDJ-1 (Hsp40). Arch Pharm Res 27, 319–323 (2004). https://doi.org/10.1007/BF02980067

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