Rare-earth element-capture peptides!

Landmodulin protein- and peptide-based ion exchange chromatography may allow the capture, separation, and purification of rare-earth elements.

According to the
U.S. Secretary of Energy Rick Perry, rare-earth elements are vital for developing and manufacturing high-tech devices, including computers, cell phones, and other similar devices. Coal samples analyzed from Illinois, Northern Appalachian, Central Appalachian, Rocky Mountain Coal Basin, and the Pennsylvania Anthracite region contained high rare-earth element concentrations at greater than 300 parts per million (ppm). However, extracting and separating individual rare earth elements from rare-earth elements containing sources is challenging.

Recently, Dong et al., in 2021, reported a water-based extraction method utilizing ion exchange column chromatography with covalently conjugated lanmodulin to capture and separate rare-earth elements. The bioconjugation of biological molecules such as proteins or peptides, as well as oligonucleotides, for example, aptamers, is now a standard method in biochemistry and biotechnology.

The research group reported that immobilized lanmodulin-based column chromatography achieved a high-purity separation of the clean-energy-critical rare-earth element (REE) pair neodymium and dysprosium (Nd/Dy) from low-grade leachate (0.043 mol % REEs) into separate fractions of heavy and light REEs (88 mol % purity of total REEs) during a single column run at high capacity.

Dong et al. performed a proof-of-concept high-purity separation between REE pairs (neodymium/dysprosium (Nd/Dy), and yttrium/neodymium (Y/Nd)) and grouped separation between heavy REEs (HREE, terbium-lutetium and yttrium (Tb–Lu + Y)) and light REEs (LREE, lanthanum-gadolinium (La–Gd)). The reported approach combines primary REE extraction from non-REEs with a secondary separation between heavy and light REEs within a single, water-based adsorption/desorption cycle.

This method simplifies further processing and provides the basis for a  protein- or peptide-based method for efficient REE extraction, concentration, and separation from both high- and low-grade rare-earth sources.

Gutenthaler et al., in 2022, showed that the four short EF-hand motif peptides behaved similarly with affinities in the micromolar range for europium (EuIII) and terbium (TbIII). However, calcium ions did not bind to the peptides, as verified with circular dichroism spectroscopy.

The researchers investigated the binding characteristics of the four peptides using isothermal titration calorimetry (ITC), time-resolved laser-induced fluorescence spectroscopy (TRLFS), and molecular dynamics (MD) simulations. The following table lists observed Kd values.

Sequences comparison of the four EF hands of Mex- and Hans-LanMs

Residues canonically involved in metal binding in EF hands are in red; Pro residues are in purple.


EF-hand motifs LanM M. extorquens


EF-hand motifs LanM H. quercus









Residues canonically involved in metal binding in EF hands are in blue; Proline residues are in purple.

The study showed that the lanthanoid affinity is also preserved in these short peptide sequences. However, the very high affinity of lanmodulin, reported to be in the picomolar range, was not observed for its EF-Hand loop peptides. The short peptides had affinities in the micromolar range, similar to the average affinity of the four calmodulin binding sites, known to also have a higher affinity for Eu(III) and Cm(III) over Ca(II).

More recently, in 2023, Mattocks et al. reported the characterization of a new lanmodulin protein from Hansschlegelia quercus the researchers called Hans-LanM. The researchers found that the oligomeric state of this protein is sensitive to the radii of rare-earth ions and that the lanthanum (III)-induced dimer is >100-fold tighter than the dysprosium (III)-induced dimer. X-ray crystal structures revealed how picometre-scale differences in the radius between lanthanum (III) and dysprosium (III) modulate the Hans-LanM’s quaternary structure through a carboxylate shift that rearranges a second-sphere hydrogen-bonding network.

The comparison of the lanmodulin sequence from Methylorubrum extorquens with the lamodulin sequence from Hansschlegelia quercus revealed a distinct metal coordination explaining Hans-LanM’s selectivity within the rare-earth elements. Structure-guided mutagenesis of a critical residue at the Hans-LanM dimer interface allowed modulation of the dimerization in solution, resulting in single-stage, column-based separation of neodymium (III)/dysprosium (III) mixtures to >98% individual element purity. Hans-LanM exists in a monomer/dimer equilibrium, modulated by the presence of the specific rare-earth ion bound.

However, for practical applications in medicine, for recycling and separation of rare-earth elements, further optimization may be needed.


EF-hand motif 

Dong Z, Mattocks JA, Deblonde GJ, Hu D, Jiao Y, Cotruvo JA Jr, Park DM. Bridging Hydrometallurgy and Biochemistry: A Protein-Based Process for Recovery and Separation of Rare Earth Elements. ACS Cent Sci. 2021 Nov 24;7(11):1798-1808. [

Gutenthaler SM, Tsushima S, Steudtner R, Gailer M, Hoffmann-Röder A, Drobot B, Daumann LJ. Lanmodulin peptides - unravelling the binding of the EF-Hand loop sequences stripped from the structural corset. Inorg Chem Front. 2022 Jun 30;9(16):4009-4021. [

Mattocks JA, Jung JJ, Lin CY, Dong Z, Yennawar NH, Featherston ER, Kang-Yun CS, Hamilton TA, Park DM, Boal AK, Cotruvo JA Jr. Enhanced rare-earth separation with a metal-sensitive lanmodulin dimer. Nature. 2023 Jun;618(7963):87-93. [

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