In one embodiment the invention provides a mutant UDP-glucose receptor (P2Y14) functionally expressed in the yeast Saccharomyces. The mutant receptors have ligand-binding properties that are useful as practical biosensors. Mutagenesis of the entire UDP-glucose receptor gene yielded receptors with increased activity but similar ligand specificities, while random mutagenesis of residues in the immediate vicinity of the ligand-binding pocket yielded mutants with altered ligand specificity. The receptor mutants can be used to detect chemical ligands in complex mixtures and to discriminate among chemically or stereochemically related compounds. Also provided are methods for combinatorial applications wherein engineered receptors can be applied, for example, in a pairwise manner to differentiate among several chemical analytes that would be indistinguishable with a single receptor.