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Biological Lanthanides, Weirdly

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I hadn’t realized it, but there are some new elements that have been added to the “essential for biochemistry” list, and they’re a bit of a surprise. (I blogged about odd metals in biology a few years ago). I would guess that anything new at this point would be a surprise – the most recent element added to such a list was cadmium, which was found to be used by some species of diatoms in 2000. That one’s weird enough already, since most of us are (or should be) strongly motivated to be exposed to as little cadmium as possible.

The latest, though, are some of the lanthanide metals, as explained in this overview. The first reports of lanthanum-containing enzymes were from 2011 in methylotroph organisms, hardy little creatures that can use single-carbon molecules like methanol and methane as their sole carbon sources. Over the next few years more groups tracked down similar proteins and were able to prove that the lanthanides were in fact essential and not just possible substitutes for more common elements. The best-characterized of these is a methanol dehydrogenase called XoxF, whose function had been unknown for many years.

The lanthanide ion is held in the active site by coordination with aspartate, glutamate, and asparagine side chains in the protein, as well as by coordination with a PQQ (pyrroloquinolinequinone) cofactor, which is used by a number of bacterial species. Whenever you see an odd element in use, there are a couple of questions that come to mind immediately: can you show that it’s been depleted in the environment around the organism? And what’s the mechanism for its uptake? In the marine methylotrophs, it has indeed been demonstrated that lanthanum, cerium, neodymium, and praseodymium were all depleted during a bloom of the organisms in response to the Deepwater Horizon oil well blowout, an effect replicated with incubation experiments.

But the lanthanide uptake pathway has not been worked out yet. There may well be compounds like the tunichromes, weird peptides from sea squirts that are believed to be involved in sequestering vanadium for the organisms from seawater (that theory, though plausible, is still under debate, since the tunichromes themselves are wildly unstable and difficult to work with). It’s for sure that there are other less-exotic biochemical metal-sequestering agents out there, particularly for iron, whose low solubility in its commonly available forms often makes it a limiting nutrient. The hunt for lanthanophores is still on, though. There are methylotrophs that have even been shown to pull Nd out of hard drive magnets, so they’ve got something worked out, for sure. (That was part of a study to see if they might be feasible rare-earth-recycling organisms, but that idea is going to need some more work, since the other metals in the magnets are not so well tolerated).

It’s interesting that chemically we tend to regard the lanthanides are pretty similar species, but that the bacteria seem to have a pronounced taste for the earlier metals as opposed to things like lutetium. Those are (generally speaking) the more abundant ones as well, so it’s quite possible that evolutionary optimization landed on those metals and has tuned things up to the point that the later ones in the lanthanide row won’t fit any more. Lanthanophore molecules that can pull off that trick would be worth seeing.

Do any higher organisms need lanthanides to survive? Do you? It doesn’t seem very likely – an attempt to locate such proteins by sequence homology had to be walked back earlier this year. But as that paper notes, lanthanum and cerium supplements have been found to stimulate growth in livestock animals (which I certainly didn’t know). It seems much more plausible, though, that those effects would be working through gut bacteria or the like. I had also not realized that lanthanum carbonate is an actual drug, given to kidney patients as a way of reducing phosphate levels (and as a tablet that’s nearly an inch wide – I hope it tastes OK to chew it). If there’s a human requirement for lanthanum, they’re at least getting plenty of it. . .


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