Emerging enzymatic strategies for the synthesis of α-tertiary amino acids.

α-Tertiary amino acids (ATAAs), featuring a fully substituted α-carbon bearing two carbon substituents, are valuable building blocks in natural products, pharmaceuticals, and agrochemicals, yet their stereoselective synthesis remains a longstanding challenge in conventional chemical synthesis. Recent advances in enzymatic catalysis have provided efficient and sustainable solutions for ATAA construction. This review summarizes the advances in enzymatic strategies for ATAA synthesis reported over the past five years, with particular emphasis on pyridoxal 5'-phosphate (PLP)-dependent enzymes and non-heme iron enzymes. We highlight newly uncovered catalytic paradigms, including asymmetric radical C-C bond formation, Mannich-type reactions, [3 + 2] annulation, oxidative decarboxylation, and nitrogen migration. Photoenzymatic approaches that enable reactivity beyond canonical enzymatic pathways are also discussed. Finally, we consider the remaining challenges in expanding the chemical space and achieving predictable stereocontrol, and emphasize the opportunities arising from enzyme discovery, directed evolution, and photoenzymatic catalysis for ATAA synthesis.