Efficient production of heat-labile enterotoxin mutant proteins by overexpression of dsbA in a degP-deficient Escherichia coli strain.

Escherichia coli heat-labile enterotoxin (LT) mutants containing Val60-->Gly or Ser114-->Lys substitutions in the A subunit do not produce the A subunit efficiently in E. coli. These mutants accumulate mostly the B pentamer devoid of the A subunit in the periplasmic space. Here we show that overproduction of the periplasmic chaperone DsbA, which is involved in disulfide bond formation, in a strain deficient in the periplasmic protease DegP allows efficient production of the mutant LT molecules. Our results suggest that the formation of the oligomeric toxin is influenced by DsbA, which helps protein folding, and by DegP, which removes the folded intermediates that can be untoxic for the cell.