Modular control of l-tryptophan isotopic substitution via an efficient biosynthetic cascade

Isotopologs are powerful tools for investigating biological systems. We report a biosynthetic-cascade synthesis of Trp isotopologs starting from indole, glycine, and formaldehyde using the enzymesl-threonine aldolase and an engineered beta-subunit of tryptophan synthase. This modular route to Trp isotopologs is simple and inexpensive, enabling facile access to these compounds.