Incorporation of amino acid analogs expands protein engineering for applications in biotechnology and therapeutics. Fluorinated amino acid analogs have been employed in protein and peptide design to improve conformational stability, self-assembly, and protease resistance. We investigate the effects of residue-specific incorporation of fluorinated phenylalanine analogs, para-fluorophenylalanine (pFF), meta- fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) into a histone acetyl transferase (HAT). The HAT protein tGcn5 is able to activate gene expression by acetylating the lysines of histone tails. Here, we explore how monofluorinated analogs influence overall stability of tGcn5 and its ability to acetylate the target histone peptide.