Highly Sensitive Detection of Tyrosine and Neurotransmitters by Stereoselective Biosynthesis and Photochemically Induced Dynamic Nuclear Polarization

Tyrosine (Tyr) is a building block of proteins and a precursor of key neurotransmitters including dopamine and epinephrine. Investigations on the metabolic fate of Tyr are hampered by poor sensitivity and resolution, hindering the diagnosis of debilitating diseases including phenylketonuria, tyrosine-hydroxylase deficiency and progressive infantile encephalopathy. Here, we show that Tyr constructs bearing either a quasi-isolated ¹H^α-¹³C^α spin pair (QISP Tyr) or natural-abundance nuclides are detected at high sensitivity and resolution in biologically relevant media by optically enhanced NMR. QISP Tyr, generated via a chemoenzymatic strategy starting from achiral materials, was quantified at 200 nM and 10 μM levels in aqueous buffer and cell extracts, respectively, via low-concentration photochemically induced dynamic nuclear polarization (LC-photo-CIDNP). Further, natural-abundance epinephrine was revealed at unprecedented 10 nM levels (1.3 nanograms), while Tyr and L-DOPA required 500 nM concentrations. In all, this study establishes the ultrasensitive atomic-resolution detection of Tyr and Tyr-related neurotransmitters by optically enhanced NMR.