Augmenting melanins with Prussian blue?

Question

Terrestrial mammals usually get their color from melanins, which makes possible a range of colors, from white to black, yellow to red, and most combinations thereof. However, some dogs appear to have gotten into some alternate pigments, possibly Prussian blue (Fe₇(CN)₁₈).

Despite being related to cyanide, Prussian blue (PB) is non toxic due to the strong iron binding... and all of its constituent elements (carbon, nitrogen, iron) are generally available to mammals. From the Dzerzhinsk dogs, we can see that expressing PB as a pigment is clearly possible. However, could "mammals"¹ use PB as a biochrome? (Note that a biochrome is specifically a pigment produced by the organism; the real life dogs are blue because they ingested PB².)

(¹ If you get hung up on Earth mammals, you're missing the point. I'm asking about a fictional reality in which there are warm-blooded, often-furry, viviparous, lactating vertebrates. Please leave your pedantry at the door and take a check-tag.)

(² To be fair, it isn't clear that the pigment in question is definitely PB, or if it's some other probably-cyanide-related pigment. Feel free to either assume it is PB, or, if you can show that some other pigment would work and produce the same effect, feel free to answer based on that.)

Specifically, these "mammals" should:

• Produce PB via biochemical processes, and without poisoning themselves in the process.
• Be capable of producing PB in addition to melanin.
• Produce a consistent amount of PB given "typical" variations in diet. (In other words, just as most real mammals don't usually change colors dramatically due to normal variation in diet, the same should hold true for PB-based coloration.)
• Be capable of producing at least enough PB to have a normal, stable concentration of PB comparable to the Dzerzhinsk dogs.

Note 1: I don't care why this happened; please assume it is the result of advanced genetic engineering, or that appropriate environmental factors exist, or whatever allows you to get past that issue. You don't need to explain what that is.

Note 2: I'm aware there have been previous, more general questions about alternate biological coloration. I'm asking specifically about Prussian blue. I am aware there are other blue biochromes which are found in nature (e.g. azulene). For the purposes of this question, I am not interested in those. I am even less interested in blue coloration from e.g. structural coloration or other non-biochrome means.

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Postmortem:

First off, thank you for some amazing answers! This got a far better response than I was expecting, and I am extremely thankful for that, especially to Willk and Justin Thyme the Second. I wish I could accept more than one answer, but ultimately I decided on Isaac Woods answer for most specifically addressing how to deal with that pesky cyanide.

Given that I explicitly stated that I don't need a naturalistic explanation, Isaac's answer seems most on point for how a sufficiently capable being might design such a process into an organism. Further, we know that mammals have access to iron, and that biological processes are capable of producing cyanide, so Isaac's answer definitely seems to pass the plausibility test.

Another note... carbon and nitrogen are readily available, but iron might be more problematic. While I did say one criteria was consistency of coloration, consistency is not constancy. Humans don't usually show a lot of color variation, but can if e.g. eating enough carrots. Moreover, we can assume that a blue critter might desire iron more than a non-blue critter and would thus tend to self-regulate. As noted, certain conditions, such as infections or a dietary iron deficiency, might cause changes, and that's okay. The keywords were "normal dietary variation" and "dramatic change in coloration".

Answer 1

Make it in follicles

Mammals already have an answer for how you use nasty toxic stuff in biochemical reactions - how we make thyroid hormones. The thyroid has many follicles: small spheres of colloid (mainly a protein called thyroglobulin), surrounded by specialized cells. These cells take up iodide from the blood, and transport it into the follicle, where it is oxidised to form elemental iodine (which you don't want anywhere near anything else in your body). This iodine is then attached to residues of the thyrogobulin to form precursor thyroid hormones. See this photo for a basic illustration of the process.

In this case, I'm imagining that the skin of this animal would be made to contain follicles, expressing the right enzymes on the follicular cells to form cyanide ions by whatever process you like, but only within the follicles. By preventing it from leaving the follicle, you protect the mitochondria that would otherwise make it insanely toxic. Add free iron, and some enzymes, and you have Prussian Blue in the right place to pigment the skin.

Answer 2

Although you have clarified that the creature does not have to be Earth-based, I am going to assume that it has to be Earth-type DNA-based.

For it to be a genetic trait, directly related to the process of genes, then it must be protein-based. Human genetics and DNA is all about the genetic code producing specific proteins. If the genetic DNA can not produce the necessary protein, it can not have the desired effect on the organism.

Proteins are made up of amino acids.

Amino acids are carbon-based.

Amino acids share a basic structure, which consists of a central carbon atom, also known as the alpha (α) carbon, bonded to an amino group

So in order to posit a DNA-mediated protein that results in a Prussia blue coloration or pigmentation, you first have to get the 'ingredients' into an amino acid, based around a carbon atom.

Since the elements in the formula for the substance creating the Prussia Blue coloration (Fe7(CN)18) are all naturally encoded in amino acids, and in fact it is already carbon-based, there does not seem to be any particular reason in genetics that what you are asking is not possible.

Although I do not know of any particular pathway to an amino acid and then a protein that would specifically result in that particular molecular structure, this part can be hand waved away. It could be possible, the details are not necessary.

Since the basic elements involved are already plentiful in the diet of a DNA-based organism, I do not see diet as an impediment.

And there does not need to be a reason for the genetic modification. It could be just a random neutral mutation that gets passed on.

EDIT

I am not sure if this helps, but Prussian Blue is used for medicinal purposes in some human illnesses.

Prussian blue is described as a deep blue pigment that is produced when the oxidation of ferrous ferrocyanide salts occurs. It contains ferric hexacyanoferrate(II) in a cubic lattice crystal structure. It is insoluble in water but also tends to form a colloid thus can exist in either colloidal or water-soluble form, and an insoluble form. It is orally administered for clinical purposes to be used as an antidote for certain kinds of heavy metal poisoning, such as thallium and radioactive isotopes of caesium. Prussian blue is included in the World Health Organization Model List of Essential Medicines as a specific antidote used in poisonings to provide symptomatic and supportive treatment. It was also administered in individuals exposed to 137-Cs+ during Goiânia accident, one of the worst radioactive contamination incidents that occured in Brazil, 1983.

Also this:

In the development of advanced photothermal therapy (PTT), there is an unmet demand for constructing novel multifunctional agent for efficient cancer therapy in a synergic manner. In this study, a system based on gelatin-stabilized Prussian blue nanoparticles with conjugated doxorubicin (PB@Gel-DOX NPs) is proposed for combined photothermal therapy and enzyme-responsive drug release for tumor destruction.

and this

The Prussian blue (PB) based nanostructure is a mixed-valence coordination network with excellent biosafety, remarkable photothermal effect and multiple enzyme-mimicking behaviours. Compared with other nanomaterials, PB-based nanoparticles (NPs) exhibit several unparalleled advantages in biomedical applications.

Second Edit

You might have a problem with bacterial infection, however. The blue skin just might turn white in the presence of bacteria.

Based on a simple sonochemical coating process, smart hospital fabrics with the capacity to detect live bacteria by a simple change of colour are presented here. Prussian Blue nanoparticles (PB-NPs) are sonochemically coated on polyester-cotton textiles in a single-step requiring 15 min. The presence of PB-NPs confers the textile with an intensive blue colour and with bacterial-sensing capacity. Live bacteria in the textile metabolize PB-NPs and reduce them to colourless Prussian White (PW), enabling in situ detection of bacterial presence in less than 6 h with the bare eye (complete colour change requires 40 h). The smart textile is sensitive to both Gram-positive and Gram-negative bacteria, responsible for most nosocomial infections. The redox reaction is completely reversible and the textile recovers its initial blue colour by re-oxidation with environmental oxygen, enabling its re-use. Due to its simplicity and versatility, the current technology can be employed in different types of materials for control and prevention of microbial infections in hospitals, industries, schools and at home.

Answer 3

Tricky, possibly to the point of notdoability

https://en.wikipedia.org/wiki/Prussian_blue

Making Prussian Blue with biochemistry would be like juggling lit blowtorches and shurikens. The raw materials are present in biological systems: cyanide can be produced by endogenous mammalian metabolic pathways and life needs iron. Prussian blue can form spontaneously at sites contaminated by industrial wastes - liberated cyanide binds with iron in the soil. So all the parts are in place.

The problem is the parts are in place in the context of delicate biological systems that will be laid waste by these parts. Cyanide is crazy toxic and super soluble and so is handled by enzymes that bind it with sulfur. Iron also is carefully handled with shepherding molecules because microbes want it and will take it if they can, and it will generate free radicals if given a chance.

I could imagine an enzyme which detoxified cyanide by complexing it with iron. Prussian Blue is not very toxic and would be a good repository. As far as I can tell, detox enzymes use sulfur or oxygen. Iron containing enzymes keep their iron and use it to generate radicals and do chemistry. The end products of these metabolic pathways do not contain iron. I think sulfur must be less expensive than iron; if you can detoxify something by binding it with iron you can probably use sulfur in a similar way and save your valuable iron.

Then I was thinking: maybe dump the cyanide into a no-mans land where there is also free iron, let the prussian blue form abiogenically like it does in soil then reclaim it. Problems: the only no-mans land available is the GI tract and it is loaded with microbes that will claim both the iron and cyanide. Also if you can absorb Prussian Blue you can probably absorb cyanide and so the cyanide will come back and hack your biology and get bound with sulfur to detoxify it.

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I could not dream up a mammalian biochemical path that was even a remote cousin of any actual mammalian biochemistry. But I would like to see one. I will put some bounty on this when I am able, to reward an answer with molecules and pathways, ideally drawn with ballpoint pen on a napkin.

Answer 4

Protective coloration!

It's a dog eat dog world out there. Several closely related species of dogs have contested the top of the food chain with one another for millions of years.

In these dogs, the epithelial cells of the skin produce large quantities of nitriles. These are produced by modifying the lysine side chains of keratin proteins in the stratum spinosum. An enzyme, maybe related to this one (I haven't accessed), has evolved to target these side chains. Using molecular oxygen, they convert the -CH2-NH2 of lysine into -CH=NH and -C≡N, releasing two molecules of H2O. These cells also produce an alternative oxidase for cyanide-resistant respiration. That reduces their metabolic efficiency, but allows them to resist high HCN levels.

As the cells begin to accumulate filaggrin (which marks the beginning of the end of their metabolic function) they activate a proenzyme which then releases HCN from the side chains through a comparably targeted reduction with NADH, which they release from their mitochondria as they inactivate alternative oxidase.

Now the result would be that the dogs would reek of cyanide gas, but they don't - it would poison them. How do they avoid this? Ferrisomes! These are small vesicles present abundantly in each cell, containing large amounts of transferrin secreted while the cells were still in the basal layer of the skin, which has accumulated large amounts of iron ions. But for some time now, the pH of these vesicles has been alkaline, denaturing the protein and releasing the Fe3+ ions. The HCN from surrounding cells enters these vesicles and is bound into ferrocyanide, which is then oxidized (maybe with molecular oxygen or NAD+) to produce ferricyanide.

The resulting epithelium therefore has outer blue layers of ferricyanide-containing vesicles. These are pretty, and pretty harmless. Unless and until they experience severe trauma, such as exposure to salivary amylase or stomach acid. Then, sodium-hydrogen antiporters built into the walls of these vesicles release an abundance of stored sodium out of the vesicle, and greatly lower its pH. This causes the ferricyanide to release HCN. Some additional HCN may be released during digestion with stomach acid. The resulting poisonous experience tends to dissuade members of related or unrelated species from consuming these animals.

Answer 5

Be Happy, Let's not be Blue!

Prussian blue, despite the name, is actually considered by some to be a shade of grey (color being highly subjective), although various preparations make it increasingly take on a bluish hue (and given the rarity of blue, it's blue-like qualities are what are considered valuable).

It currently isn't produced biologically, so there is no biochemical pathway as of now. So if you want it, you need to handwave it into existence. But once you handwave, all your problems are solved. There is nothing intrinsically wrong with Prussian blue except it has no precedent.

Not the answer you're looking for: The easiest excuse is animals eating foods containing it, produced by some fictional plant that produces it (this is akin to your Dzershinsk dogs). Mammals don't tolerate cyanide intermediate compounds well, and are unlikely to develop independent production due to the toxic intermediaries. Plants use various means to make themselves resistant to cyanide, so they are your best starting point. If your animals need something but don't produce it themselves, it is really no different than a vitamin - an essential compound like vitamin C obtained from food. We obtain lots of vitamins in stable quantities from our food.

The answer you're looking for: There are animals that do tolerate cyanide in special ways, however, so nothing is impossible. Depending on your fictional biochemistry, it could even be toxic to some organisms and not others. For example, tomatoes are related to belladonna, and tomatine (found in tomatoes) is poisonous and/or distasteful to some insects. Given a strong selective reason for your animals to develop cyanide-based biochemistry, it is unlikely but not impossible that they produce Prussian blue initially as a byproduct, but eventually on purpose as a color. Keep in mind, however, that the blue color is only useful/serves a purpose if the organism can see blue (not a forgone conclusion) or if blue is an attractant for prey, a repellant for predators, or allows your animal to blend into their environment (and if the environment is blue, getting PB from foods is a lot more plausible).