Impact of a Biological Chelator, Lanmodulin, on Minor Actinide Aqueous Speciation and Transport in the Environment.

Minor actinides are major contributors to the long-term radiotoxicity of nuclear fuels and other radioactive wastes. In this context, understanding their interactions with natural chelators and minerals is key to evaluating their transport behavior in the environment. The lanmodulin family of metalloproteins is produced by ubiquitous bacteria and lanmodulin (LanM) was recently identified as one of nature's most selective chelators for trivalent f-elements.

Correction: Radiolabeling and evaluation of lanmodulin with biomedically relevant lanthanide isotopes.

[This corrects the article DOI: 10.1039/D3CB00020F.].

Radiolabeling and evaluation of lanmodulin with biomedically relevant lanthanide isotopes.

Short-lived, radioactive lanthanides comprise an emerging class of radioisotopes attractive for biomedical imaging and therapy applications. To deliver such isotopes to target tissues, they must be appended to entities that target antigens overexpressed on the target cell's surface. However, the thermally sensitive nature of biomolecule-derived targeting vectors requires the incorporation of these isotopes without the use of denaturing temperatures or extreme pH conditions; chelating systems that can capture large radioisotopes under mild conditions are therefore highly desirable.

Enhanced rare-earth separation with a metal-sensitive lanmodulin dimer.

Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number. The natural lanthanide-binding protein lanmodulin (LanM) is a sustainable alternative to conventional solvent-extraction-based separation. Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer.

A genetically encoded fluorescent sensor for manganese(II), engineered from lanmodulin.

The design of selective metal-binding sites is a challenge in both small-molecule and macromolecular chemistry. Selective recognition of manganese (II)-the first-row transition metal ion that tends to bind with the lowest affinity to ligands, as described by the Irving-Williams series-is particularly difficult. As a result, there is a dearth of chemical biology tools with which to study manganese physiology in live cells, which would advance understanding of photosynthesis, host-pathogen interactions, and neurobiology.

Engineering lanmodulin's selectivity for actinides over lanthanides by controlling solvent coordination and second-sphere interactions.

Developing chelators that combine high affinity and selectivity for lanthanides and/or actinides is paramount for numerous industries, including rare earths mining, nuclear waste management, and cancer medicine. In particular, achieving selectivity between actinides and lanthanides is notoriously difficult. The protein lanmodulin (LanM) is one of Nature's most selective chelators for trivalent actinides and lanthanides.

Bridging Hydrometallurgy and Biochemistry: A Protein-Based Process for Recovery and Separation of Rare Earth Elements.

The extraction and subsequent separation of individual rare earth elements (REEs) from REE-bearing feedstocks represent a challenging yet essential task for the growth and sustainability of renewable energy technologies. As an important step toward overcoming the technical and environmental limitations of current REE processing methods, we demonstrate a biobased, all-aqueous REE extraction and separation scheme using the REE-selective lanmodulin protein. Lanmodulin was conjugated onto porous support materials using thiol-maleimide chemistry to enable tandem REE purification and separation under flow-through conditions.

Capturing an elusive but critical element: Natural protein enables actinium chemistry.

Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying and limited knowledge of Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here, we demonstrate a straightforward strategy to purify medically relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry, using the recently discovered protein, lanmodulin.

Characterization of Americium and Curium Complexes with the Protein Lanmodulin: A Potential Macromolecular Mechanism for Actinide Mobility in the Environment.

Anthropogenic radionuclides, including long-lived heavy actinides such as americium and curium, represent the primary long-term challenge for management of nuclear waste. The potential release of these wastes into the environment necessitates understanding their interactions with biogeochemical compounds present in nature. Here, we characterize the interactions between the heavy actinides, Am and Cm, and the natural lanthanide-binding protein, lanmodulin (LanM).

Determination of affinities of lanthanide-binding proteins using chelator-buffered titrations.

The recent discoveries of the first proteins that bind lanthanides as part of their biological function not only are relevant to the emerging field of lanthanide-dependent biology, but also hold promise to revolutionize the technologically critical rare earths industry. Although protocols to assess the thermodynamics of metal-protein interactions are well established for "traditional" metal ions in biology, the characterization of lanthanide-binding proteins presents a challenge to biochemists due to the lanthanides' Lewis acidity, propensity for hydrolysis, and high-affinity complexes with biological ligands. These properties necessitate the preparation of metal stock solutions with very low buffered "free" metal concentrations (e.

Heterologous expression, purification, and characterization of proteins in the lanthanome.

Recent work has revealed that certain lanthanides-in particular, the more earth-abundant, lighter lanthanides-play essential roles in pyrroloquinoline quinone (PQQ) dependent alcohol dehydrogenases from methylotrophic and non-methylotrophic bacteria. More recently, efforts of several laboratories have begun to identify the molecular players (the lanthanome) involved in selective uptake, recognition, and utilization of lanthanides within the cell. In this chapter, we present protocols for the heterologous expression in Escherichia coli, purification, and characterization of many of the currently known proteins that comprise the lanthanome of the model facultative methylotroph, Methylorubrum extorquens AM1.

Biological, biomolecular, and bio-inspired strategies for detection, extraction, and separations of lanthanides and actinides.

Lanthanides and actinides are elements of ever-increasing technological importance in the modern world. However, the similar chemical and physical properties within these groups make purification of individual elements a challenge. Current industrial standards for the extraction, separation, and purification of these metals from natural sources, recycled materials, and industrial waste are inefficient, relying upon harsh conditions, repetitive steps, and ligands with only modest selectivity.

Selective and Efficient Biomacromolecular Extraction of Rare-Earth Elements using Lanmodulin.

Lanmodulin (LanM) is a recently discovered protein that undergoes a large conformational change in response to rare-earth elements (REEs). Here, we use multiple physicochemical methods to demonstrate that LanM is the most selective macromolecule for REEs characterized to date and even outperforms many synthetic chelators. Moreover, LanM exhibits metal-binding properties and structural stability unseen in most other metalloproteins.

A Selective, Protein-Based Fluorescent Sensor with Picomolar Affinity for Rare Earth Elements.

Sensitive yet rapid methods for detection of rare earth elements (REEs), including lanthanides (Lns), would facilitate mining and recycling of these elements. Here we report a highly selective, genetically encoded fluorescent sensor for Lns, LaMP1, based on the recently characterized protein, lanmodulin. LaMP1 displays a 7-fold ratiometric response to all Lns, with apparent Ks of 10-50 pM but only weak response to other common divalent and trivalent metal ions.

Lanmodulin: A Highly Selective Lanthanide-Binding Protein from a Lanthanide-Utilizing Bacterium.

Lanthanides (Lns) have been shown recently to be essential cofactors in certain enzymes in methylotrophic bacteria. Here we identify in the model methylotroph, Methylobacterium extorquens, a highly selective Ln-binding protein, which we name lanmodulin (LanM). LanM possesses four metal-binding EF hand motifs, commonly associated with Ca-binding proteins.