A family portrait of lanmodulin selectivity for enhanced rare-earth separations

Diep, P.; Madsen, C. S.; Choi, W.; Dong, Z.; Kang-Yun, C. S.; Uychoco, P. F. V.; Seidel, J. A.; Eaton, S. A.; Jiao, Y.; Cotruvo, J. A.; Park, D. M.

doi:10.64898/2026.01.22.699517

bioRxiv · 10.64898/2026.01.22.699517

A family portrait of lanmodulin selectivity for enhanced rare-earth separations

Diep, P.·Madsen, C. S.·Choi, W.·Dong, Z.·Kang-Yun, C. S.·Uychoco, P. F. V.·Seidel, J. A.·Eaton, S. A.·Jiao, Y.·Cotruvo, J. A.·Park, D. M.

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Abstract

Proteins offer a molecular design space to create bespoke ligands for the separation of critical metals, like rare earth elements (REs). However, data-intensive approaches to fine-tune metalloprotein selectivity are bottlenecked by the low-throughput nature of existing characterization methods. Here we invented an assay called SpyTag-Catcher Immobilization of Lanmodulin for Assaying Metal-Binding Selectivity (SpyCI-LAMBS) to measure metalloprotein selectivity en masse. This 96-format workflow was used to study the selectivity of 621 lanmodulin (LanM) orthologs for 15 REs, revealing eight distinct selectivity profiles based on sequence-to-function analyses. We discovered >200 LanMs with dampened selectivity for low-value LaIII relative to the prototypical LanM. This includes a LanM that can perform a challenging one-stage separation of PrIII from LaIII with up to >99.9 mol% purity and 83% yield. SpyCI-LAMBS is a powerful tool that can rapidly collect high-fidelity selectivity data to inform metal ion separations and machine learning-assisted metalloprotein design.

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Diep, P., Madsen, C. S., Choi, W., Dong, Z., Kang-Yun, C. S., Uychoco, P. F. V., Seidel, J. A., Eaton, S. A., Jiao, Y., Cotruvo, J. A., Park, D. M.. 2026-01-23. A family portrait of lanmodulin selectivity for enhanced rare-earth separations. https://doi.org/10.64898/2026.01.22.699517

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