We present an economic and straightforward method to introduce 13 C- 19 F spin systems into the deuterated aromatic side chains of phenylalanine as reporters for various protein NMR applications. The method is based on the synthesis of [4- 13 C, 2,3,5,6- 2 H 4 ] 4-fluorophenylalanine from the commercially available isotope sources [2- 13 C] acetone and deuterium oxide. This compound is readily metabolized by standard Escherichia coli overexpression in a glyphosate-containing minimal medium, which results in high incorporation rates in the corresponding target proteins.