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. 2024 Jun 3;17(6):e14503. doi: 10.1111/1751-7915.14503

Rare earth elements in biology: From biochemical curiosity to solutions for extractive industries

Raquel A Rocha 1,2, Kirill Alexandrov 1,3,4, Colin Scott 1,2,✉
PMCID: PMC11146143  PMID: 38829373

Abstract

Rare earth elements (REEs) are critical for our modern lifestyles and the transition to a low‐carbon economy. Recent advances in our understanding of the role of REEs in biology, particularly methylotrophy, have provided opportunities to explore biotechnological innovations to improve REE mining and recycling. In addition to bacterial accumulation and concentration of REEs, biological REE binders, including proteins (lanmodulin, lanpepsy) and small molecules (metallophores and cofactors) have been identified that enable REE concentration and separation. REE‐binding proteins have also been used in several mechanistically distinct REE biosensors, which have potential application in mining and medicine. Notably, the role of REEs in biology has only been known for a decade, suggesting their considerable scope for developing new understanding and novel applications.

To meet society's demands for technologies that use rare earth elements (including those that allow a decarbonized society), we need to increase the volume and efficiency of extraction by mining and recycling. Microbial rare earth biochemistry offers numerous enabling biotechnologies to achieve this.

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INTRODUCTION

Rare earth elements (REEs) include the 4f‐block lanthanide series (atomic number 57–70) and three d‐block elements: lutetium, scandium and yttrium (Cheisson & Schelter, 2019). With broad applications in electronic components, catalysts, lasers, glass, medicine and permanent magnets, REEs are becoming increasingly important to the global economy, with global production of REEs growing from 100,000 metric tonnes in 2015 to 300,000 metric tonnes in 2022 (Liu et al., 2023). The growth in this market is in part due to the need for permanent magnets in the clean energy technologies needed to achieve the UN goals on decarbonization (e.g., electric motors and generators).

While termed rare earths, these elements are not especially scarce, indeed some REEs are more abundant on Earth than many commonly mined metals (such as copper and gold). Instead, the name rare earth reflects the relative difficulty involved with the extraction of these metals. High energy costs and the use of harsh chemicals in the extraction of REEs can result in significant environmental consequences. The presence of actinides in lanthanide‐bearing soils and ores also leads to significant quantities of radioactive waste (Golroudbary et al., 2022). Moreover, the demand for REEs, especially praseodymium, neodymium and dysprosium, is expected to outpace our ability to supply these elements using our current mineral deposits and extractive technologies (IEA, 2021). One possibility is that the increasing demand for REEs may be partially met by exploiting waste streams, including mining tailings and recycling streams, effectively circularizing the REE economy, and only needing to satisfy the shortfall caused by the increase in demand for REEs (Wang et al., 2024).

Regardless of the source of REEs, new technologies will be needed to improve the environmental and economic sustainability of REE supply (Ye, Jin, et al., 2023). Within this context, the recent advances in our understanding of the function of REEs in biology are particularly interesting. Until the discovery of REE‐dependent methanotrophic bacteria in 2005, REEs were not thought to have a role in biological systems. The molecular basis for REE dependency was described in 2011, when a novel periplasmic, pyrroloquinoline quinone (PQQ)‐dependent methanol dehydrogenase (XoxF) was discovered. XoxF performs a critical step in methylotrophy by oxidizing methanol to produce formaldehyde. Unlike the previously characterized methanol dehydrogenases, XoxF incorporates REEs into its PQQ‐pincer cofactor, rather than a Ca2+ cation (Nevarez et al., 2020). Since these initial discoveries, there has been a considerable advance in our understanding of the role of REEs in biology and the potential biotechnological opportunities that may arise. In this review, we cover what has been discovered about bacterial REE physiology and some of the emerging technologies that are based on recent innovations in this fascinating new field.

PHYSIOLOGICAL ROLE OF RARE EARTH ELEMENTS

A biological role for REEs was discovered due to their essential role for the growth of polyextremophilic methylotrophs (Methylacidiphilum fumariolicum) isolated from volcanic mud from the Solfatara crater in Italy (Pol et al., 2007). Their role in the PQQ‐dependent methanol dehydrogenase of this organism was later elucidated (Keltjens et al., 2014). The M. fumariolicum methanol dehydrogenase (XoxF), which converts methanol to formaldehyde in the second step of methylotrophy (Figure 1). Formaldhyde is then either assimilated as biomass or converted to CO2. XoxF is a homologue of MxaF, the well‐studied Ca2+ and PQQ‐dependent methanol dehydrogenase; however, XoxF uses an REE anion in place of Ca2+ (Figure 2).

FIGURE 1.

FIGURE 1

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Schematic depicting methylotrophy. The term methylotrophy refers to the use of reduced C1 compounds, particularly methane and methanol, as a source of energy and/or carbon by eubacteria and archaea (Claassens et al., 2018; Khmelenina et al., 2019). The carbon from these reduced C1 compounds can be fully oxidized to CO2 to provide energy or assimilated into biomass via the serine cycle, tricarboxylic (TCA)/Krebs cycle and ethylmalonyl CoA pathway (EMCP). Oversupply of carbon via methyltrophy can lead to the formation of carbon storage polymers (e.g., polyhydroxybutyrate; PHB) (Khanna & Srivastava, 2005; Lee, 1996; Ray et al., 2023). Figure created with BioRender.com.

FIGURE 2.

FIGURE 2

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A comparison between the calcium and REE‐dependent methanol dehydrogenases (MxaF and XoxF) from M. extorquens. Cartoon representations of monomers of MxaF and XoxF are shown, with PQQ (cyan) shown in the central cavity of the β‐propellor bound to their cognate metals: calcium (blue sphere) or REE (sand coloured sphere). A more detailed view of the metal coordination is shown below, PQQ provides three coordinating bonds in both cases. For calcium in MxaF, there are three additional amino acid residues as ligands, while in XoxF there are four. Created with BioRender.com.

In both cases, the metal is coordinated by a cofactor (PQQ) in what has been described as a pincer, one of two pincer‐type cofactors known in nature (Nevarez et al., 2020). The nickel pincer, found in lactate racemase, is a modified planar nicotinamide cofactor that binds nickel via tridentate coordination. PQQ‐type pincers are also planar, using the ribosomally synthesized and post‐translationally modified peptide (RiPP) PQQ to tri‐coordinate a metal (Gao et al., 2024). PQQ‐pincers have been shown to bind calcium, magnesium and REEs (Anthony & Ghosh, 1998; Matsushita et al., 2002; Nevarez et al., 2020). Interestingly, it had been known for some time before the discovery of XoxF that MxaF proteins containing metals other than Ca2+ (such as strontium and yttrium) possess catalytic activity, albeit at a far lower catalytic rate than the Ca2+‐containing holoprotein (Adachi et al., 1990).

Structures of XoxF from several organisms (e.g., M. fumariolicum, Methylomicrobium buryatense and Methylacidimicrobium thermophilum) have been solved (Deng et al., 2018; Jahn et al., 2018; Schmitz et al., 2021), with the monomer consisting of an eight‐bladed β‐sheet propeller, in which the PQQ‐pincer is bound in the central cavity of the monomer. In broad terms, the mechanism of methanol dehydration is thought to proceed via deprotonation of the substrate by an active site carboxylate group, which acts as a general base. The bound metal acts as a Lewis acid, polarizing the hydride‐accepting oxygen/carbon bond, enabling the reaction to proceed via either a substitution/elimination or a hydride transfer mechanism (Figure 3). PQQ is reduced to PQQH2 process, which then undergoes two single‐electron transfers to an appropriate electron acceptor (e.g., cytochrome cL (Beardmoregray et al., 1982)). While both the substitution/elimination and the hydride transfer mechanisms are both plausible, the detail of the reaction remains unresolved (Sarmiento‐Pavía & Sosa‐Torres, 2021).

FIGURE 3.

FIGURE 3

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PQQ‐dependent methanol oxidation. (A) The PQQ‐metal (M) complex oxidizes methanol to formaldehyde in a two‐electron transfer that results in PQQH2 (altered bonds highlighted in pink). Two successive electron transfers to a suitable electron acceptor (e.g., Cytochrome CL) allow the reoxidation of PQQH2 to PQQ. There are two proposed mechanisms for the oxidation of methanol. (B) An addition‐elimination reaction, which involves the production and subsequent elimination of a tetrahedral intermediate, and (C) a hydride transfer mechanism that requires an enolization step to form PQQH2. For both (B) and (C) the metal (shown as Ca2+ in this case) acts as a Lewis acid that helps to stabilize the charges developed across the reactive carbon–oxygen bond.

Perhaps surprisingly, rather than being restricted to a somewhat obscure group of extremophilic methanotrophs, putative REE‐dependent methanol dehydrogenases have been described in a broad range of Gram‐negative bacteria from a range of environmental niches (Chistoserdova, 2017; Howat et al., 2018; Kato et al., 2020; Picone et al., 2021; Ramachandran & Walsh, 2015; Tani et al., 2021; Thulasi et al., 2018). Phylogenetic analysis of the XoxF/MxaF family showed that there are six clades, five XoxF clades and a single MxaF clade. All five XoxF clades contained a D‐x‐x‐D‐[YFW]‐D motif, the final aspartate residue of which was shown to coordinate the REE cation in the crystal structures and distinguishes XoxF from MxaF (Chistoserdova, 2011; Keltjens et al., 2014). Constant with the phylogenetic analysis, the replacement of this aspartate residue with a serine residue in the XoxF from M. extorquens yielded an inactive protein (Good et al., 2020). The D‐x‐x‐D‐[YFW]‐D motif was also found in two ADH‐type alcohol dehydrogenases (ExaF/PedH). The two enzymes from Pseudomonas putida and M. extorquens have REE‐dependent ethanol dehydrogenases (Wehrmann et al., 2017). Interestingly, XoxF‐type dehydrogenases have also been found in the genome of the archaeal phylum Thaumarchaea (Aylward & Santoro, 2020). This suggests that REE biochemistry may substantially contribute to bacterial and archaeal carbon metabolism and more broadly to the global carbon cycle (Ramachandran & Walsh, 2015; Taubert et al., 2015).

UPTAKE, BIOACCUMULATION AND HOMEOSTASIS OF REEs

Knowledge concerning the mechanism(s) of sensing, regulation, uptake and storage of REE in bacteria is still limited, although there has been significant progress over the last few years.

Probably the best understood component of REE uptake is the small protein lanmodulin (LanM; Figure 4). LanM is a small, periplasmic protein that was first identified when it co‐purified with the XoxF protein from M. extorquens (Cotruvo et al., 2018). LanM belongs to the same protein family as calmodulin, the well‐studied calcium‐sensing protein (Kursula, 2014). The structure of LanM complexed with REEs shows that the four EF‐hand domains responsible for binding calcium in calmodulin were also present in LanM, consistent with a metal‐binding function, but that the cation is coordinated by six amino acid residues, compared with five as is the case for calmodulin.

FIGURE 4.

FIGURE 4

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Known natural chelators of REEs. Cartoon representations of the two known protein‐based chelators of REEs (lanmodulin, lanpepsy) are shown. Calmodulin is also shown as a comparison with lanmodulin. EF hands from calmoduin and lanmodulin are shown with calcium (blue sphere) and an REE (sand coloured sphere) shown, along with their cognate ligands (sticks). The acidic residues in the central cavity of lanpepsy are also shown as sticks. The small molecule metallophore identified from M. extorquens, methylolanthanin, is also shown. Created with BioRender.com.

LanM has been shown to have a high affinity for REEs (K D values in the low picomolar range for yttrium and the lanthanides), eight orders of magnitude lower than the K D value for calcium. The LanM from M. extorquens has greatest affinity for Sm, Nd and La (Cotruvo et al., 2018). The affinity seems to be related to the atomic radius of the cation, with the larger REEs binding with greater affinity (Roszczenko‐Jasinska et al., 2020). More recently, sequence similarity network analysis revealed that the LanM homologues could be clustered, with M. extorquens‐type LanM proteins forming a large cluster, but with several additional clusters (Mattocks et al., 2023). The cluster containing the Hansschlegelia quercus LanM was distinct from the M. extorquens‐type LanM proteins and contained LanM homologues from the genera Hansschlegelia, Xanthobacter, Ancyclobacter, Oharaeibacter, Methylopila and Starkeya. While the relationship between atomic radius and K D values first observed in M. extorquens LanM was retained in the H. quercus LanM, there was a larger difference in the K D values of Nd and Dy than was observed in the M. extorquens ortholog. Notably, while the M. extorquens LanM forms a monomer, the H. quercus LanM is dimeric (Mattocks et al., 2023). The consequences of dimerization of LanM (if any) on the K D, cooperativity of binding, metal selectivity, etc. are not understood at the time of writing this review.

The periplasmic location of LanM led to speculation that its physiological role is to scavenge REEs for use in enzymatic functions (e.g., XoxF and ExaF) (Cotruvo et al., 2018). However, it should be noted that strains with lanM deletions did not exhibit obvious phenotypes during REE‐dependent growth, which may imply that LanM fulfils a different role (Fujitani et al., 2022). The phylogenetic distribution of LanM is also somewhat limited compared to the distribution of XoxF‐like proteins (found only in Methylobacterium, Methylorubrum and Bradyrhizobium species), suggesting that there may be alternative REE scavengers (whether protein or small molecule metallophores) in other genera (Daumann et al., 2022).

Interestingly, a second small, periplasmic binding protein, lanpepsy (LanP; Figure 4), has been identified in Methylobacillus flagellates (Hemmann et al., 2023). While M. flagellatus is an obligate methylotroph and possesses XoxF‐like dehydrogenase genes, it does not contain homologues of LanM. Proteomic analysis of the REE‐dependent response of M. flagellatus revealed the upregulation of several proteins, including XoxF, its cognate cytochrome C, a TonB‐dependent receptor and two putative transcriptional regulators (Hemmann et al., 2023). Two further proteins were identified: a putative metal efflux protein from the CusA‐family (Mfla_0908) and a putative periplasmic protein that contained two PepSY protease domains (Mfla_1052, LanP). While PepSY proteins are typically thought of as proteases, there is evidence that they possess a diversity of functions that include siderophore reduction (Josts et al., 2021) and uranium binding (Gallois et al., 2022). Binding studies suggest that each LanP monomer binds four REE cations with high specificity and selectivity, with low μM KD values for a range of REEs. Alpha‐fold modelling revealed that the core of LanP is highly acidic, suggesting that this is the location of the cation‐binding sites in lanpepsy, albeit empirical determination of apo‐ and holo‐LanP structures will be needed to fully understand the protein: cation interactions (Hemmann et al., 2023).

Evidence for specific REE uptake systems has been acquired for M. extorquens, based on genetic analysis and electron microscopy (Roszczenko‐Jasinska et al., 2020). The hypothesis generated from these studies suggested that a small molecule metallophore, at the time unidentified, acts as an REE scavenger which is transported into the periplasmic space via a TonB‐dependent transport protein (LutH). The periplasmic protein LutA then carries the loaded metallophore to LutEF, an ABC transporter, which delivers the REE‐loaded metallophore to the cytoplasm.

More recently, transcriptomic analysis of this strain allowed the identification of a small molecule chelator for REEs, methylolanthanin (Figure 4), which is structurally related to the Rhodopseudomonas palustris siderophore, rhodopetrobactin (Zytnick et al., 2023). A biosynthetic cluster for methylolanthanin (mllABCDEFGHJ) has been identified and encodes an abs‐like biosynthetic cluster. The role this operon in REE acquisition was confirmed in a deletion strain that had a reduced capacity to accumulate REEs, while over‐expressing the mll genes in trans increased the accumulation of REEs (Zytnick et al., 2023). An operon adjacent and divergent from the mll operon was identified that encodes a TonB‐dependent transport protein, a sigma factor and an anti‐sigma factor. This operon was termed the methylolanthanin uptake operon (mluARI), and likely facilitates transport of loaded methylolanthanin and regulates the expression of at least some genes involved in uptake and use of REEs (Zytnick et al., 2023).

There is also evidence that M. extorquens and other methanotrophs accumulate REEs. In M. extorquens, intracellular granules formed when grown in REE‐rich medium. The granules were visualized using transition electron microscopy and further analysis revealed that the granules are crystalline, quite likely composed of polyphosphate salts of the imported REE (Roszczenko‐Jasinska et al., 2020). Alternative REE storage mechanisms seem to exist; for example, at least one strain of the methylotroph Beijerinckiaceae appears to store REEs in outer membrane vesicles (Wegner et al., 2020, 2021).

How REE homeostasis is achieved remains an open question. However, there are some clues concerning potential transcriptional regulators that may be involved in coordinating the cellular response to the presence of REEs. The mluR and mluI genes of M. extorquens encode a putative sigma/anti‐sigma factor pair (Zytnick et al., 2023). Sigma factors and their cognate anti‐sigma factor partners are often employed to regulate the expression of genes, with the sigma factor directing RNA polymerase to promoters with orthogonal/non‐canonical promoters and anti‐sigma factors sensing extracellular stimuli that modulate the activity of the sigma factor (Campbell et al., 2008; Hughes & Mathee, 1998).

More evidence for complex gene regulation in M. extorquens was revealed in a mutant that was shown to hyper‐accumulate REEs, including heavy lanthanides (which the wild‐type strain does not). The mutant also displayed an increase in metallophore production and altered phosphate metabolism. These changes were attributed to a point mutation in a histidine kinase/regulator (Good et al., 2022). Finally, there is some evidence that mutations in a gene encoding lunase in Methylomicrobium buryatense lead to changes in the transcription of REE‐related genes (Chu et al., 2016).

POTENTIAL APPLICATIONS

One of the more obvious applications that flow from the discoveries described above is the concentration and separation of REEs from complex mixtures, such as mine tailings, medical and electronics waste, low‐grade ore, and contaminated materials (Figure 5) (Martinez‐Gomez et al., 2016). Methylotrophs that accumulate REEs provide a mechanism for the accumulation of REEs. A recent report demonstrated that it was possible to use M. extorquens to accumulate neodymium from magnet waste (swarth) and improve the accumulation level by optimizing the culture medium used. A similar approach has been used to reclaim/remediate gadolinium (a highly toxic medical imaging agent) from medical waste (Good et al., 2022). Notably, hyperaccumulating mutants of M. extorquens have been identified, potentially allowing the development of more efficient REE bioextraction processes (Good et al., 2023). Another promising approach has been to engineer the capability to accumulate REEs into a range of microorganisms (E. coli, Caulobacter crescentus, Yarrowia lipolytica, and Acidithiobacillus ferrooxidans) by the heterologous expression of lanmodumin targeted to their periplasmic space (Brewer et al., 2019; Chang et al., 2020; Jung et al., 2023; Park et al., 2020; Xie et al., 2022). The modified A. ferrooxidans is of particular note, as the chassis organism grows in the low pH conditions (<2) needed to solubilize REEs (Jung et al., 2023).

FIGURE 5.

FIGURE 5

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Bio‐inspired REE concentration and separation technologies. (A) Concentration of REEs via bioaccumulation by live bacteria and storage (intracellular polyphosphate/REE crystals are shown). (B) Chromatographic separation and concentration of REEs, using immobilized REE‐binding molecules (lanmodulin shown). (C) Selective precipitation of REEs with PQQ. Created with BioRender.com.

The use of high‐affinity REE binders as chromatography agents has also been investigated (Figure 5). Lanmodulin has been the subject of several studies in which the protein from M. extorquens or H. quercus has been immobilized on agarose beads, magnetic nanoparticles or natural structural proteins (e.g., elastin‐like polypeptides) (Hussain et al., 2022; Mattocks et al., 2023; Ye, Wang, et al., 2023). This approach has been successful in extracting REEs from a range of complex materials. A similar approach has also been used for short oligopeptides with sequences derived from EF hands (Hostert et al., 2023). The K D of EF hands out of their natural context is higher than when in lanmodulin, presumably partially due to the cooperativity observed for the EF hands in the intact protein (Gutenthaler et al., 2022). However, oligopeptide‐based systems can be used in the separation of REEs from a complex mixture (Hostert et al., 2023). A separation approach using the cofactor PQQ has also been trialled (Figure 5). Because PQQ‐REE complexes are practically insoluble, it is possible to precipitate REEs out of solution by adding PQQ (Lumpe et al., 2020). Interestingly, lanmodulin also has low K D values for actinides, equivalent to or lower than for the REEs, suggesting that some of the technologies being developed for REEs may also be applicable for 5f‐block elements as well as the 4f‐block lanthanides (Deblonde, Mattocks, Dong, et al., 2021; Deblonde, Mattocks, Wang, et al., 2021; Singer et al., 2021).

Finally, sensing REEs represents a substantial opportunity in mining, medicine, and waste treatment. Lanmodulin has been adapted for sensing applications (Figure 6). In the first approach, LanM has been fused with fluorescent proteins for use as a FRET‐based biosensor exploiting the large conformational change in the protein associated with metal binding. Biosensors based on this approach have been shown to have picomolar K D values for REEs (Mattocks et al., 2019). Interestingly, this FRET‐based biosensor has also been re‐engineered to detect manganese, indicating that EF hands may have the capacity to be tuned to a range of cations (Park et al., 2022). A second approach uses the natural luminescence of some lanthanides (e.g., Tb3+ and Eu3+) (Featherston et al., 2021). It isn't possible to stimulate luminescence in these cations using light directly (as it involves an f‐f transition), and so a photosensitiser (a tryptophan residue) was introduced into the EF hand in proximity to the bound REE to promote luminescence resonance transfer. This luminescence‐based biosensor was shown to detect low nM concentrations of Tb3+ acid mine drainage water (Featherston et al., 2021). In another iteration of REE biosensor design, the calmodulin‐based GCaMP has been reengineered to sense REE by replacing calcium‐binding EF hands with EF hands from lanmodulin via point mutation (Jones et al., 2024). GCaMP is a circularly permutated GFP with myosin light chain (M13) and calmodulin fused to the N and C‐termini, respectively. Binding of calcium causes a change in confirmation of calmodulin that promotes high‐affinity binding of M13. The β‐barrel of the GFP in the absence of calcium allows water to enter the central cavity and protonation of the fluorophore. Binding calcium reversibly alters the confirmation of the GFP β‐barrel leading to desolvation, and consequent deprotonation, of fluorophore. This leads to a substantial increase in fluorescence (Akerboom et al., 2009; Schreiter et al., 2009). The REE‐sensing variant of GCaMP (termed LanTERN) has been shown to sense a range of REEs at low μM K D values, which imparts a ~ 15‐fold increase in fluorescence (Jones et al., 2024).

FIGURE 6.

FIGURE 6

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Bio‐based REE sensors. (A) Fluorescence resonance energy transfer (FRET) sensor. Lanmodulin (purple) is fused with donor and recipient fluorescent proteins at its N‐ and C‐termini. REE binding causes a conformational change to lanmodulin that brings the two fluorescent proteins within the Forster distance (minimal permissive distance for resonance). (B) Luminescence‐based sensing. Luminescence can be induced in some REEs (e.g., terbium) using an antenna (e.g., a tryptophan residue engineered into the EF hand of lanmodulin). (C) The LanTERN sensor, based on the GCaMP calcium sensor. The metal‐bound conformation (bottom) promotes the formation of a complex between the fused myosin light chain (orange) and calmodulin (sand), which excludes water from GFP, enhancing its fluorescence. In the absence of metal (top), water can access the GFP β‐barrel, reducing its fluorescent output. Created with BioRender.com.

OUTLOOK

M. extorquens has become the de facto model organism for studying the role of REEs in biology and has yielded a wealth of insights into REE‐related molecular biology over the last decade. However, there are still substantial gaps in our fundamental understanding of REE biochemistry. The details concerning how REEs are scavenged, trafficked and stored, and how homeostasis is achieved and regulated in M. extorquens is still incomplete. There is also substantial evidence that there are mechanistic differences in these processes between REE‐using genera, suggesting that learnings from M. extorquens may not serve as a model for other species, including archaea.

Several biotechnologies have the potential to address issues relating to REE extraction and recycling through their concentration and separation. These technologies have been shown to work well at bench scale, but only one study to date addressing the issue of scalability (Good et al., 2023). In addition to scalability, technoeconomic and life cycle analyses will be required to demonstrate that these biotechnologies can compete with existing extraction methods, both from an economic and environmental perspective. If GMOs or gene edited microbial strains are to be used, containment and regulatory compliance may also become important.

Beyond applications in the extractive industries, it is notable that REEs are also versatile catalysts, participating in oxidations (including photoactivated oxidation), asymmetric hetero‐Diels–Alder additions, hydroelimination, and C‐X bond formation (Dicken et al., 2021; Qiao & Schelter, 2018). While artificial enzymes capitalizing on the catalytic versatility of REEs have been engineered (Caldwell et al., 2020; Klein et al., 2024), to date the only naturally occurring biochemical role for REEs identified is in alcohol oxidation. Characterization of the lanthome (REE‐induced proteins) may identify new REE‐dependent enzymes. Moreover, host strains that take up REEs will simplify the engineering and production of natural and artificial REE‐dependent enzymes, potentially expanding applications for REEs in biocatalysis. In addition to catalysis, high‐affinity biocompatible chelators for REEs and actinides have potential applications in medical imaging, theragnostics, targeted alpha therapies and other medical interventions. It is likely that the potential applications identified here are simply the most obvious, and additional innovations will emerge in the near future.

AUTHOR CONTRIBUTIONS

Raquel A. Rocha: Conceptualization; writing – original draft; writing – review and editing. Kirill Alexandrov: Conceptualization; writing – review and editing. Colin Scott: Conceptualization; writing – original draft; writing – review and editing; supervision; project administration; funding acquisition.

FUNDING INFORMATION

No funding information provided.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no conflict of interest.

ACKNOWLEDGEMENTS

RAR was supported by a CSIRO Research Plus Postdoctoral Award.

Rocha, R.A. , Alexandrov, K. & Scott, C. (2024) Rare earth elements in biology: From biochemical curiosity to solutions for extractive industries. Microbial Biotechnology, 17, e14503. Available from: 10.1111/1751-7915.14503

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