An α-amino group is not absolutely required for A domain substrate activation: in fact, many NRPS enzymes activate monomers containing an α-hydroxy functional group. However, only one α-hydroxy acid A domain has ever been crystallized to date, and it was an engineered variant of TycA from tyrocidine biosynthesis (Figure ). The authors used combinatorial mutagenesis and yeast cell surface display selection for the high-throughput generation of TycA variants with preferential selectivity for phenyllactic acid (PLA) over the native L-Phe substrate.