The Liu lab engages with metals, unraveling their role in conducting the life-sustaining chemistry of amino acids. Bridging the realms of chemistry and biology, we delve into diverse themes such as enzymatic symphonies, oxygen’s activation tango with metalloproteins, and the intricate sculpting of C–H/C–F bonds. Our curiosity spans the vibrant palette of natural product biosynthesis, the delicate choreography of protein cofactor assembly, and the free radical orchestration driven by enzymes. We tune into the murmurs of metal-mediated redox sensing and signal transduction. To illuminate these concealed worlds, we employ diverse chemical and biophysical techniques: crafting small molecule mechanistic probes through synthesis, capturing insights through EPR, ENDOR, NMR, and resonance Raman spectroscopies, dissecting molecules with LC-MS and calorimetry, seizing fleeting moments with freeze-quench and in crystallo chemical reactions, examining protein structures with X-rays, and rewriting the genetic code to incorporate non-canonical (unnatural) amino acids into proteins. Through this comprehensive exploration, we paint a vivid portrait of the metal-mediated amino acid enchantment that underlies life itself.