Expanding metabolism for total biosynthesis of the nonnatural amino acid L-homoalanine.

ABSTRACT: The dramatic increase in healthcare cost has become a significant burden to the world. Many patients are denied the accessibility of medication because of the high price of drugs. Total biosynthesis of chiral drug intermediates is an environmentally friendly approach that helps provide more affordable pharmaceuticals. Here we have expanded the natural metabolic capability to biosynthesize a nonnatural amino acid L-homoalanine, which is a chiral precursor of levetiracetam, brivaracetam, and ethambutol. We developed a selection strategy and altered the substrate specificity of ammonium-assimilating enzyme glutamate dehydrogenase. The specificity constant k(cat)/K(m) of the best mutant towards 2-ketobutyrate is 50-fold higher than that towards the natural substrate 2-ketoglutarate. Compared t

SUBMITTER: Zhang K 

PROVIDER: S-EPMC2852006 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature