Biochemical approaches of expanding the genetic code dramatically increase the methodologies available to manipulating protein structure and function. The introduction of fluorinated amino acids into proteins has been used to design proteins with improved thermal stability and increased resistance to denaturants. Histone acetyltransferases (HATs) represent a group of proteins that acetylate the lysine residues on histone tails using acetyl coenzyme A. The molecular basis for HAT specificity was conducted on Tetrahymena Gcn5 (tGcn5) in complex with its substrates by Poux and Marmostein. Our goal is to explore the effects fluorinated amino acids have on the stability and function of HAT tGcn5. In this study, we have biosynthetically replaced phenylalanines in tGcn5 with a series of fluorinated analogs: p-fluorophenylalanine (pFF), o-fluorophenylalanine (oFF), and m-fluorophenylalanine (mFF). We demonstrate high levels of substitution and investigate its effects on protease degradation and activity for the target H3p19 substrate.