Suppressing posttranslational gluconoylation of heterologous proteins by metabolic engineering of Escherichia coli.

ABSTRACT: Minimization of chemical modifications during the production of proteins for pharmaceutical and medical applications is of fundamental and practical importance. The gluconoylation of heterologously expressed protein which is observed in Escherichia coli BL21(DE3) constitutes one such undesired posttranslational modification. We postulated that formation of gluconoylated/phosphogluconoylated products of heterologous proteins is caused by the accumulation of 6-phosphogluconolactone due to the absence of phosphogluconolactonase (PGL) in the pentose phosphate pathway. The results obtained demonstrate that overexpression of a heterologous PGL in BL21(DE3) suppresses the formation of the gluconoylated adducts in the therapeutic proteins studied. When this E. coli strain was grown in high-cell-de

SUBMITTER: Aon JC 

PROVIDER: S-EPMC2258596 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature