Composition and methods for the production of L-homoalanine

摘要

Healthcare costs are a significant worldwide, with many patients being denied medications because of their high prices. One approach to addressing this problem involves the biosynthesis of chiral drug intermediates, an environmentally friendly solution that can be used to generate pharmaceuticals at much lower costs than conventional techniques. In this context, embodiments of the invention comprise methods and materials designed to allow microorganisms to biosynthesize the nonnatural amino acid L-homoalanine. As is known in the art, L-homoalanine is a chiral precursor of a variety of pharmaceutically valuable compounds including the anticonvulsant medications levetiracetam (sold under the trade name Keppra®) and brivaracetam, as well as ethambutol, a bacteriostatic antimycobacterial drug used to treat tuberculosis. Consequently, embodiments of the invention can be used in low cost, environmentally friendly processes to generate these and other valuable compounds.

主权项

1. A composition of matter comprising a mutant glutamate dehydrogenase polypeptide having enzymatic activity to convert 2-ketobutyrate to L-homoalanine and comprising an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 1, wherein the amino acid residue corresponding to position K92 of SEQ ID NO: 1 is mutated to L or V and the amino acid residue corresponding to position T195 of SEQ ID NO: 1 is mutated to A or S in the mutant glutamate dehydrogenase polypeptide.