Rational improvement of simvastatin synthase solubility in Escherichia coli leads to higher whole-cell biocatalytic activity.

ABSTRACT: Simvastatin is the active pharmaceutical ingredient of the blockbuster cholesterol lowering drug Zocor. We have previously developed an Escherichia coli based whole-cell biocatalytic platform towards the synthesis of simvastatin sodium salt (SS) starting from the precursor monacolin J sodium salt (MJSS). The centerpiece of the biocatalytic approach is the simvastatin synthase LovD, which is highly prone to misfolding and aggregation when overexpressed from E. coli. Increasing the solubility of LovD without decreasing its catalytic activity can therefore elevate the performance of the whole-cell biocatalyst. Using a combination of homology structural prediction and site-directed mutagenesis, we identified two cysteine residues in LovD that are responsible for nonspecific intermolecular cros

SUBMITTER: Xie X 

PROVIDER: S-EPMC3928684 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature