beta-Amino acids are rapidly growing in importance as a key class of pharmaceutical intermediates, with applications in a number of current and future drugs. This Phase 1 proposal seeks to establish the feasibility of a novel and broadly applicable method for the production of chiral beta-amino acids. In the first step, the chemical synthesis of a series of substituted 5,6-dihydrouracils from inexpensive and readily available starting materials will be demonstrated and optimized. In the second step, the substituted 5,6-dihydrouracil precursors will be converted in a single step to beta-amino acids by the action of two enzymes working in concert: a dihydrouracilase, which will cleave the dihydrouracil ring hydrolytically to produce an N-carbamoyl beta-amino acid, followed by a carbamoylase, which will produce the desired beta-amino acid. BioCatalytics currently has four dihydrouracilase enzymes for testing in the proposed method. The gene encoding the carbamoylase will be cloned into E. coli and produced in the course of the project. The efficacy of the method will be demonstrated by producing gram quantities of four current commercial target beta-amino acids.
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