The invention provides nitrilases and methods for making and using them, and in one aspect, provides methods for producing enantiomerically pure α-substituted carboxylic acids, such as, for example, α-amino acids and α-hydroxy acids. In one aspect, methods of the invention combine an aldehyde or ketone with a cyanide and ammonia or an ammonium salt or an amine, in the presence of a nitrilase or a polypeptide having nitrilase activity, to stereoselectively hydrolyze the amino nitrile or cyanohydrin intermediate under conditions sufficient to produce the carboxylic acid.