Mining peptides for mining solutions: evaluation of calcium-binding peptides for rare earth element separations

Rare earth elements (REEs), which include the 15 lanthanides plus scandium and yttrium, are critical components commonly used in permanent magnets and play a significant role in electronics and green energy technologies. Due to the similarities of these ions, conventional separation processes are chemically- and energy-intensive and generate large quantities of waste. The lanthanides share physical and chemical similarities with calcium ions, which allow REEs to replace calcium in calcium-binding peptides and proteins. In this study, we conducted a bioinformatic search to identify calcium-binding peptides with high affinity to bind and separate REEs. Seven unique domains representing different calcium-binding geometries were selected for evaluation. The results revealed a strong correlation between the charge of the binding loop and its affinity for REEs. We concluded that highly charged, aspartic acid-rich loops exhibit greater electrostatic repulsion, which creates higher affinity due to the increased stabilization effect of ion binding. Binding affinity across the lanthanide series was highest for ions with radii similar to that of calcium (∼1 Å), consistent with the evolutionary optimization of calcium-binding proteins for selective ion recognition. While selectivity varied among proteins in solution, immobilized proteins demonstrated higher selectivity toward intermediate REEs. One notable candidate identified in the bioinformatic search was HEW5 from <i>Nocardioides zeae</i>. We leveraged the selectivity of HEW5 in a 7 mL column to demonstrate a single-stage, chelator-free separation of an equimolar lanthanum-neodymium mixture, achieving a high purity (>90%) and yield (90%) of REEs. Additionally, immobilized HEW5 was used to remove non-REE ions from a simulated leachate stream and separate lanthanum (>90% purity) from other REEs in a single separation stage.