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How Many Things Can Be Enzymes, Anyway?

For many years, enzymes were thought to be basically the only biological catalyst molecules out there. Then things like ribozymes were discovered, and it was appreciated that the nucleic acid polymers could also bind substrates and catalyze their reactions. That brought up a natural question: what other sorts of complex polymers might be able to do the same thing? Proteins can clearly do a terrific job, but is that because they’re clearly the best choice, or just the one that evolutionary biochemistry landed on?
That’s a hard question to answer, but it covers a lot of important ground. Can enzyme-like catalysts be made from chemically more robust scaffolds? These could be of great industrial use – proteins don’t stand up to very much rough handling. And since catalysis would seem essential for living systems, how many alternatives are there for extraterrestrial chemical-based life? Those may not be too far off of what we know, but still be strange to us: we find amino acids, nucleotides, and simple carbohydrates in carbonaceous solar system debris, so they would appear to be produced by the sorts of processes (heat, pressure, irradiation) involved in the formation of planetary systems. And they may well form the most likely building blocks for life in general, assuming that we’re not particularly special. But did we have to end up with ribose, 2-deoxyribose and the four nucleotides we have (or our twenty-ish amino acids?)
Maybe not, according to this new paper. The authors describe several new “synthetic generic polymers“, with new and completely unnatural carbohydrate backbones, and show that these, too, can fold into catalytic species. Random pools of these polymers were selected out to find ligase and endonuclease activity:

We have shown the discovery of catalysts (RNA endonucleases) in four such XNA sequence spaces (ANA, FANA, HNA, CeNA) and the elaboration of three different catalytic activities (RNA endonuclease, RNA ligase and XNA ligase) in one (FANA). These results indicate that properties such as catalysis (as well as heredity and evolution) are generalizable to a range of nucleic acid scaffolds and are likely to be emergent properties of many synthetic genetic polymers. This argues against a strong functional imperative for the chemistry of life’s genetic systems.

Indeed it does. A few billion years of selection pressure on any of these, one imagines, might well produce biochemistries just as robust as ours. And how many more are possible? We might eventually find that life in the universe might be, in general, sort of like us (DNA-ish genetics to make protein-ish molecules, decorated with carbohydrate-y surfaces), but very different in the particulars. I hope we get a chance to find out.
As an aside, this sort of thing brings up a thought that has occurred to me many times about extraterrestrial life: if it does tend to be broadly similar to us, biochemically, might it not also be the source of wildly potent allergans allergens? A few science-fiction writers have speculated about this, but most popular treatments tend to ignore this possibility, for obvious dramatic reasons: imagine Kirk and Spock beaming down to the surface of a new planet, greeting the natives, and then swelling up while collapsing in sneezing fits. . .

22 comments on “How Many Things Can Be Enzymes, Anyway?”

  1. Richard Thomas says:

    A wildly potent allergEn is indeed a scary thought. A wildly potent allergAn might just reinvigorate the pharmaceutical industry.

  2. This has always been one of my personal crackpot thoughts about extra-terrestrial scifi: even assuming a technically breathable atmosphere as seen on a chromatograph, there’s no reason to assume that humans wouldn’t go into anaphylactic shock the instant they took a couple of deep breaths of a foreign biosphere. Even taking a plane ride across the USA is cause for some people to stock up on the prescription antihistamines; lord knows what our immune systems would make of genuinely alien proteins.
    And allergic reactions might be the relatively manageable part of the problem: the unicellular biome of any world with an even slightly harsher set of selection pressures than ours might well out-compete our own gut and blood flora (or even our mitochondria if they could manage to pass the cell wall) for basic resources inside our own bodies, with results that would be fascinating to watch… from several thousands of miles away via remote camera.
    A couple of SF books that do actually play around with this concept: Peter Watts’ “Rifters” series (Starfish, ß-Max and ßehemoth), and “Bios”, one of Robert Charles Wilson’s earlier novels.
    (Of course, the opposite could just as easily be true: earth’s unicellular critters, which we would necessarily import by the trillion into any ET biosphere, might turn out to be effective apex predators of the local flora and fauna, triggering a die-off that would make the columbian introduction of smallpox to South America look relatively innocuous in comparison. )

  3. Derek Lowe says:

    #1 – I think I’ll just call that one a Freudian slip. . .

  4. Anonymous says:

    People rarely have anaphylactic responses to something the first time they encounter it, and people don’t by default don’t exhibit anaphylaxis every time they are exposed to a new substance. Not sure why this would be such an issue on another planet.

  5. lt says:

    I always figured that any small group of atoms, suitably arranged in space, could be an enzyme. The scaffold doesn’t seem all that important for activity. As atoms are the same everywhere I wouldn’t expect extremely novel and potent extraterrestrial allergens to be very common – surely there are more similarities than differences.

  6. oncodoc says:

    Even if the planet is loaded with busty green-skinned women, it always struck me as strange that one wouldn’t wear protective gear on first contact. Alien emanations might provoke catastrophic immune mediator responses without previous inoculation, or the saliva of the green-skinned hotties might be full of curare like compounds. There are a lot of fun speculations to make.

  7. Tim R says:

    Ironically, does this mean the Space Hippies episode could be the MOST accurate of all Star Trek episodes? Never mind The Borg, Herbert, those flowers will kill you.

  8. Anonymous says:

    Protein backbones are rarely involved directly in catalytic activity, but their overall flexibility and regular hydrogen bonding are critical for folding into diverse shapes. So as long as you have a regular backbone with similar flexibility and hydrogen bonding potential, and a diverse array of side chains, then I don’t see why any other polymer couldn’t fold to form a potent and specific enzyme.

  9. NMH says:

    @7 If was acidity in the fruit in that episode, not allergens, you hipster.

  10. Sam Adams The Dog says:

    The good news is that if such beings ever invade us, we won’t be very good food for them. OTOH, they might devour our entire carbohydrate supply.

  11. Nile says:

    Frank Herbert’s Dune has a zone of dead and decaying vegetation where the introduced terrestrial flora runs up against the native biome: I recall reading the throwaway phrase “amino acid incompatibility”.
    Given the vast number of small amino acids that can exist, it’s certain that a different repertoire to our familiar twenty-one would be in use by *closely* similar biomes; and it is very likely that we would be mutually toxic.
    Wildly-differing biomes are another bet entirely. I think that amino acids and protein chains would be ubiquitous – Carbon, Nitrogen, Oxygen and Hydrogen are the commonest available elements everywhere – but I can imagine an alien biosphere utilising a lot more phosphorus, or even an organic halogen or two.
    Both would likely be very toxic indeed: well up into nerve-gas territory.
    As for Earthbound organisms being out-competed by an extraplanetary interloper, I would draw to your attention the absurd inefficiency of Rubisco. If alien life exists at all, it will almost certainly be capable of taking over as the primary photosynthesizer and, on the balance of probabilities, it will not be accessible to the terrestrial food chain as a ‘producer’.
    So we had better hope that one or more of our amino acids is violently toxic to all unknown life.

  12. Anonymous says:

    @11: “I would draw to your attention the absurd inefficiency of Rubisco”
    Can you or anyone else come up with something better?

  13. tcc says:

    Assume you had a bag money to invest in coupling chemistries for an origin of life…assume you didn’t know about proteins, could you have predicted that our amino acids could fold up into wondrous things like GPCRs, antibodies, mysoin and hemoglobin?
    You have a much better chance of winning the lottery than finding a random amino acid sequence that folds!

  14. Allchemistry says:

    “Can enzyme-like catalysts be made from chemically more robust scaffolds”.
    I think that conformational flexibility, which causes the structural instability, lies at the very heart of the extraordinary catalytic flexibility of proteins. In general, I really cannot think of any other class of polymers which could match proteins in regards to their amazing functional versatility.

  15. Allchemistry says:

    “Can enzyme-like catalysts be made from chemically more robust scaffolds”.
    I think that conformational flexibility, which causes the structural instability, lies at the very heart of the extraordinary catalytic flexibility of proteins. In general, I really cannot think of any other class of polymers which could match proteins in regards to their amazing functional versatility.

  16. Sipi says:

    Life on Earth works in and with water as a solvent and reaction partner. For me the real question is whether life could eveolve in other solvests. That would be really different chemistry.

  17. Anonymous says:

    @13: “You have a much better chance of winning the lottery than finding a random amino acid sequence that folds!”
    Not sure that’s true, at least not if you count aggregation as a form of intermolecular folding. Also, remember that many/most proteins are able to fold properly only because they are made in isolation, from one end, otherwise they tend to aggregate if you just try to fold the complete molecules all together in one pot.

  18. Pedantic Spaker says:

    Regarding the “enzyme” question, I have actually thought that we should refer to protein enzymes as “proteozymes” and expand the definition of “enzyme” to all catalyst biomolecules.

  19. tcc says:

    @17 it is certainly true, all sorts of polymers aggregate, I’m only referring to things that fold into discrete, soluble structures in standard conditions.
    Find a structure of a protein sequence (i.e. reasonably long > 30aa, and that David Baker’s group did not find) that isn’t closely related to a natural sequence.

  20. M Bower says:

    Our protein enzymes can do a fair number of things with the sidechain chemistries they have – nucleophilic attack especially – but for really rich biochemistry they rely on a host of cofactors. I might expect an alien biochemistry to include some of those kinds of functions in its enzymatic polymers – something flavin-like to handle one- and two-electron oxidations and reductions, for example, and maybe a chelating sidechain to hold certain metal atoms in place rather than a porphyrin.

  21. cometaryorbit says:

    I think it would be *very* hard for alien microbes to outcompete our gut flora etc, as our gut flora has adapted to the human environment and alien microbes wouldn’t have.
    Over centuries or millennia of humans living exposed to an alien biosphere, something like that might happen, but it would take some serious evolution, I think. And maybe not even in millennia, depending on how different the biochemistries were.
    Allergies could certainly happen, but I don’t see why it should be especially common or severe.

  22. li zhi says:

    Seems to me that foreigners will be unlikely to thrive in either ecosystem. (Us on a alien planet, the alien planet’s microbes in us.) But, there probably is significant risk of one or the other ecology containing a species which the other ecology finds is uncontrollable. Remember the isolation procedures required for our lunar astronauts? But its a good point that we’d not want to kill off an entire planet’s ecosystem (nor our own). Not that we’re likely to get the chance anytime soon, LOL! (The more different the conditions are, the less likely anything in our ecology will be better adapted, fwiw). Oh, a related thought – there is an interesting TED talk (the Great Filter or Something out there is going to kill you, Sept ’14) as referenced on Marginal Revolution:

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