I don’t think I need to convince you of the benefits of biodiversity, but we just learned a new way to eliminate skunk odor from a mushroom.
That mushroom, Tolypocladium, is pictured above, courtesy of the Western Pennsylvania Mushroom Club, and if you don’t mind, I would like to take a moment to commend Western Pennsylvania for having a Mushroom Club.
Tolypocladium has needed to defend itself from pests out there for a very long time. Bacteria would love to devour it, and those bacteria are always coming up with new chemicals to make life difficult for other organisms. We humans struggle with anthrax, botulism, tetanus, and many other bacterial maladies, but mushrooms have their own set of bacterial toxins to worry about.
Dr. Robert Cichewicz’s lab at the University of Oklahoma has been studying Tolypocladium for awhile, and they got their species of it from a crowdsourcing project where people submitted soil samples from odd places. They found, back in 2016, that one Alaskan fungus (that turned out to be Tolypocladium) started making a new compound when it was exposed to bacteria, presumably to defend itself. So they set out to find what that compound was, and why it was there.
The new compound kept reacting with a bunch of things in the culture to form all sorts of derivatives, but after sifting through all of these, Cichewicz and crew were able to deduce the original product made by the fungus, and it’s called pericosine A:
That chlorine (Cl) atom in green likes to hog negatively charged electrons for itself (hey, that’s just how chlorine is), and that leaves the carbon atom next to it with a positive charge. Positive attracts negative, of course, so that positive charge can seek out another molecule with a negative hotspot. When they collide, you can get an exchange where chlorine is bumped off and the new molecule gets attached. For this reason, the authors describe pericosine A as an “electrophilic warhead”!
Many of the antifungal compounds that bacteria make (Antifu?) are susceptible to attack by our little “warhead”. So the authors assembled a group of antifungals, and sure enough, several of them were neutralized by pericosine A. Two really great examples were the well-known antifungals ciclopirox and anisomycin. These are toxic in the parts-per-million range to many fungi.
Pericosine A gleefully reacted with both of these and wiped out their antifungal activity entirely. The results are just what you’d expect if chlorine gets replaced one-for-one by these molecules, and the products are nontoxic clunkers:
There are a lot of ways to resist antibiotics, but this was a trick that no one had seen before: sending out small molecules as independent agents to go on the attack. Sneaky little mushrooms.
But that brings us to 2019, and the skunks!
Now we have a new paper from the Cichewicz lab which also includes authors Lin Du, Charissa Munteanu, Jarrod King, and Doug Frantz.
As they explain, the main agents of stink in skunk spray are thiols, as you see below.
Thiols in general are notoriously smelly. They’re spiked into natural gas in tiny quantities to alert you to a leak, because their rotten-egg stench is so potent.
I should point out here, in a “Why Organic Chemistry Is Fun” moment, that if you replace the sulfur atom in 3-methyl-1-butanethiol with an oxygen atom, you get fake banana flavor (isoamyl alcohol)! Why would these two super-similar chemicals smell so gobsmackingly different? Well, nobody knows, really.
Anyway, given the structure of thiols, with another electron-hogging atom, sulfur (S), ripe for attack by an “electrophilic warhead”, our researchers thought it was worth a shot to see if something could be done about them.
You and I are not organic chemists, but I think we can now guess what happens when pericosine A meets skunktastic chemical (E)-2-buten-1-thiol:
And that wipes out the odor of the thiol completely:
[T]he effectiveness of the reactions at neutralizing the odor of skunk-gland secretions was readily apparent to the research team: whereas even single-digit microliter volumes of the skunk scent were capable of creating an overwhelmingly foul aroma (even when briefly removed from the chemical fume hood), samples of skunk secretions that had been properly treated with pericosine A [...] could be handled on the benchtop for extended periods without emitting any trace of unpleasant odor.
You might wonder how hard it is to make pericosine A, but as often happens in biochemistry, the mushrooms just repurposed a molecule they were already very good at making. It’s called shikimic acid, and it normally goes on to become the amino acids tryptophan, tyrosine, and phenylalanine. You can’t have protein without those, so this is a robust thing.
Plants use shikimic acid, too, to ultimately make lignin, and they make a crapload of it. It’s part of their basic structure, and it keeps water from seeping out and pests from getting in (its breakdown products are toxic to insects and bacteria). Plants string these kinds of molecules together in complicated ways to make their lignin:
So on the plus side for pericosine A, it shouldn’t be too hard to make (and there are probably cheaper analogs to be developed that work just as well). It also meets the specs for an “ultramild” chemical, showing no irritating or mutagenic effects. It does great at removing skunk odor when it’s dissolved in propylene glycol, an inexpensive and nontoxic liquid used widely in cosmetics.
On the minus side, the chemical industry is as unforgiving as the wild, and scientific success by no means guarantees a commercial product. (But you needn’t worry too much, because you can always fall back on baking soda and peroxide to get rid of skunk odors.)
That’s not the main point here, though. This seemingly silly story has an awful lot underpinning it. A new class of natural products. A new mechanism for resisting antibiotics. A better understanding of what factors are important in the dynamics of ecosystems. We need to preserve our biodiversity for a million reasons like this.
But if we get a new deskunkifying ointment out of the whole thing, I’ll take it!