A key limiting factor for dietary use of single cell protein is the high mass fraction of nucleic acid, which limits daily consumption due to uric acid production during metabolism. High rates of RNA synthesis are unfortunately necessary for high protein productivity.
The paper notes:
>It is important to note that MP products often contain elevated levels of nucleic acids, constituting ~8% of the dry weight [17], which necessitates consideration when assessing their suitability for human consumption. To address this, a heat treatment process is employed at the end of fermentation that reduces the nucleic acid content in the fermented biomass to below 0.75/100 g, while simultaneously deactivating protease activity and F. venenatum biomass. However, this procedure has been observed to induce cell membrane leakage and a substantial loss of biomass, as evidenced in the Quorn production process [17], which also utilizes F. venenatum as the MP producer. Our experimental trials have encountered similar challenges, achieving a biomass yield of merely ~35%, and observed that heating process increased the relative protein and chitin content (Figure 2D,E), which may be related to the effect of membrane leakage, while the intracellular protein of the FCPD engineered strain was less likely to be lost to the extracellular. Thus, concentrating the fermentation broth to enhance protein and amino acids content in successive steps to produce a highly nutritious water-soluble fertilizer appears to be an effective strategy for adding value to the process (Figure 1).
The challenges of developing economic single cell protein products, that are suitable for human consumption, are described in chapter 3 here:
There are better alternatives than consuming the whole cells.
There have been other attempts to use genetically-modified fungi (Trichoderma) for protein production, where they secrete in the cultivation medium a water-soluble animal protein, e.g. a cow whey protein or chicken egg white protein.
Then, through filtration and ultrafiltration, the desired protein is separated from the fungal cells and the cultivation medium, producing a protein powder in the same way how one makes whey protein concentrate or milk protein concentrate.
If done correctly this method produces only healthy protein without contaminants.
However, searching right now online if there has been any progress with this, I see that against a startup company that has already produced such whey protein powder from a fungal culture there is a lawsuit that alleges that they have not separated properly the whey protein and that what they have sold contained more fungal protein of uncertain quality and safety than the good whey protein that they claimed to sell.
Even if that company might be guilty of trying to exploit the technology before being perfected, the principle is sound and there is no doubt that this can be done, producing pure high-quality protein.
I actually use whey protein concentrate to provide a significant fraction of my protein consumption, so I hope that its production from fungi will succeed in a not too distant future.
Trichoderma is among the fungi that secrete enzymes in their environment, so the genetic modification that replaced its enzyme with whey protein or egg albumin is much simpler than the many modifications described in the parent article in order to make the whole cells more palatable, without really achieving this.
For producing a protein powder that can be used as an ingredient in cooking food from vegetable sources, the approach used with Trichoderma is sufficient. The techniques used in the parent article are justified because they do not want to make a healthy food, but they want to make a meat imitation. For myself, enhancing the quality of vegetable food is a much more important goal than attempting to simulate meat, but at least in USA it is likely that the second goal might make more money.
>> There have been other attempts to use genetically-modified fungi (Trichoderma) for protein production, where they secrete in the cultivation medium a water-soluble animal protein
Honest question, what does "animal protein" mean here in regards to it being produced by a fungi? is it that it's the same as as one from a cow at the molecular level?
Yes, they have replaced the gene used to synthesize the fungus protein that was secreted in the environment with a cow gene or a chicken gene.
So the cow lactoglobulin or chicken ovalbumin produced by the fungus is chemically identical to that from the protein powders that are currently made from cow milk or whey or from chicken egg white.
That means that such fungus-produced protein has an optimal amino acid profile, unlike the natural fungal proteins and if it forms a part of the daily protein intake (e.g. around a third) it can compensate the inadequate amino acid profiles of vegetable proteins.
For about 4 years I have eaten only vegetable proteins, but this created some constraints in what I could eat that were too inconvenient, so eventually I gave up. While now most of my protein intake remains of vegetable origin, I use some whey protein powder in the cooking of certain foods, to enhance their protein content, which has enabled me to make much more varied choices in the menu. Therefore I would know how to use such a product from fungi, if it would become widely available. There are a few startups in this domain, both in USA and in Europe, but for now their target is mostly in selling to big industrial producers of food, not at retail.
>against a startup company that has already produced such whey protein powder from a fungal culture there is a lawsuit that alleges that they have not separated properly the whey protein and that what they have sold contained more fungal protein of uncertain quality and safety than the good whey protein that they claimed to sell.
Sounds like par for the course in the VC-backed startup world
Seriously, I love software but a geneticist/biologist would have been a fascinating career.
DNA, evolution, etc. is insanely powerful and you are kind of reverse-engineering and tweaking it to get different outcomes, but like you point out it is very slow. We just need to live for like 10,000 years and then a lifetimes work would become more exciting.
Also it's a multi-species mutation that stuck in humans and the great apes which broke the urate oxidase enzyme.
If we fixed it, nobody would get gout.
I kinda wonder sometimes why medicine doesn't try to fix some of these species level genetic problems more broadly or more quickly. There's this enzyme every other mammal produces, why isn't there a fast track to engineering a micro-organ to produce it or inject an engineered version in gout patients (I did some research and yes people are somewhat doing these things... slowly)
Why can't I, a healthy adult, be genetically engineered to start producing my own Vitamin C like every other mammal?
It's a cool video but it's formatted almost like a tutorial, with folks in the comments appearing excited to actually try it on their own bodies with lab equipment they have access to. It's pretty irresponsible given that I don't think he fully expressed the risks of doing this to your own body.
It's not just risky, it's hard to know if it really "worked" for many reasons.
This is why we run double-blind, randomized control trials- to be convinced that the treatment "worked".
I would love for my gout to be genetically engineered away.
I didn't have a flare up until my late 20s but it finally explained the very slight ache in my big toe. After the first one, the second and third happened within a year. I stopped drinking almost entirely aside from some gin a few times a year.
I reduced various food consumption with no change. Whisky/beer will cripple me if I have more than one of either. After some research, vegan marathon runners are even plagued by this.
I second Allopurinol. Your doctor will try to tell you gout is due to your diet and lifestyle. The reality is (according to nearly everyone who actually has gout on the internet) that you just _have gout_ - you can’t diet it away.
I cut out all drinking and went vegetarian after a gout diagnosis and still had flare ups. I never drink sugary drinks or eat fast food, and yet doctors would constantly recommend cutting these out and “lifestyle changes”.
Allopurinol is the only thing keeping me from being bedridden on days I can feel a flare up.
Evolution isn’t stupid … it’s not a random outcome that we don’t produce our own vitamin c, or have an appendix, or (urate oxidize blah blah).
I wish you all the luck in fixing these problems and would be fascinated to see the outcomes… However, this notion that these changes would be cost free is a mistaken one.
Mutants with these characteristics have certainly existed over evolutionary time… Our version outcompeted them.
Evolution does not optimize for quality of life. And evolution certainly creates some pretty stupid outcomes, as it favors slapping on quick fixes at random rather than intelligently engineering the problem away. So we have hardware problems like our blind spots that got 'fixed' in software, unlike other species that evolved eyes separately and happened to get the wiring right.
Evolution also isn't smart. Have so much of something in your diet and you'll tend to lose the ability to manufacture it because there's little evolutionary pressure to maintain it. If you're a VitaminCless mutant you don't die and your children survive just fine and suddenly this becomes common in the species.
It didn't get lost because it was advantageous for it to be gone, it just wasn't important enough to get maintained.
WRT genetic engineering, I believe the main barrier to these things is that our genes are quite multipurpose. You may turn on the ability to produce vitamin C, and that same sequence of genes could also turn your eyeballs into calcified lumps.
Eh, while that's true for many things, there are plenty of genetic diseases for which it is not ("diseases" or whatever you might call the human lack of vitamin C synthesis)
In this case the gene encoding L-gulonolactone_oxidase is broken, and that's the last step in the process. That gene catalyzes something into a substance which decays into vitamin C.
Extract tissue from patient, build a cell line, CRISPR in vitro, build a cell line, sequence to verify. Use verified cell line to build pseudo-organs or to inject cells or stem cells.
This is why I said build a cell _line_, i.e. cells that all come from a single parent cell. Clones. Make monoclonal stem cell lines, use CRISPR on them, make a NEW monoclonal cell line post-CRISPR and pull some cells to validate success or failure.
When choosing what my life's work would be, I filtered out tasks that involved genetically engineering humans so that my solution cold compete with "eating a nice, fresh orange". Maybe I'm just lazy and unambitious.
Whatever engineered solution could happen, it will almost certainly have more side effects than a diet that includes vitamin C, and even if not, cost way more.
> Therapeutically, recombinant urate oxidase (like rasburicase or pegylated urate oxidase) is used as a medication to rapidly lower uric acid levels, treating tumor lysis syndrome, hyperuricemia, and gout, especially when other treatments fail or are contraindicated.
Wikipedia:
> It has been proposed that the loss of urate oxidase gene expression has been advantageous to hominoids, since uric acid is a powerful antioxidant and scavenger of singlet oxygen and radicals. Its presence provides the body with protection from oxidative damage, thus prolonging life and decreasing age-specific cancer rates.[15]
> Children with non-Hodgkin's lymphoma (NHL), specifically with Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (B-ALL), often experience tumor lysis syndrome (TLS), which occurs when breakdown of tumor cells by chemotherapy releases uric acid and cause the formation of uric acid crystals in the renal tubules and collecting ducts. This can lead to kidney failure and even death. Studies suggest that patients at a high risk of developing TLS may benefit from the administration of urate oxidase.[17] However, humans lack the subsequent enzyme HIU hydroxylase in the pathway to degrade uric acid to allantoin, so long-term urate oxidase therapy could potentially have harmful effects because of toxic effects of HIU.[18]
> Higher uric acid levels have also been associated with epilepsy. However, it was found in mouse models that disrupting urate oxidase actually decreases brain excitability and susceptibility to seizures.[19]
> Graft-versus-host disease (GVHD) is often a side effect of allogeneic hematopoietic stem cell transplantation (HSCT), driven by donor T cells destroying host tissue. Uric acid has been shown to increase T cell response, so clinical trials have shown that urate oxidase can be administered to decrease uric acid levels in the patient and subsequently decrease the likelihood of GVHD.[20]
> Urate oxidase is formulated as a protein drug (rasburicase) for the treatment of acute hyperuricemia in patients receiving chemotherapy. A PEGylated form of urate oxidase, pegloticase, was FDA approved in 2010 for the treatment of chronic gout in adult patients refractory to "conventional therapy".[21]
As a general rule though, you can effectively treat/prevent gout by significantly increasing consumption of water and by replacing proteins with cereal grains (or fruits and vegetables or vegetable fats). These are inexpensive, fairly safe solutions.
Ha, didn't expect to see a comment about Mullen on HN. Saw him live in Boston a few months ago. Very cool to see the C-Town boys blowing up in popularity.
Firefox for Android is some of the worst software I've ever used. A lot of extensions won't work in it, and even Edge Canary is far better with them. It is extremely slow, and the UI is horrible.
I'm running it on a device with a Qualcomm SM8635 Snapdragon 8s Gen 3 chipset, and it just crawls. The UI is very unresponsive, and page load times are terrible. It also has to reload the page if it was running in the background and you switch back to it.
Strange, I am running it on a Snapdragon 8 Gen 2 (Z Fold 5), and it's totally fine for me. (If anything, it's a little too good at staying in the background; if you have private tabs open it insists on persisting in memory.)
Not saying your issues aren't real, but rather maybe there's another app or your manufacturer's flavor of Android that's causing the issue (like those aggressive background killers).
As for Edge, I used to be a big fan, but when they finally introduced history and tab syncing in 2021, it didn't have E2EE, and it still doesn't, which I find inexcusable. All the other major browser vendors offer it, even Google (though you have to opt in).
I'm running it on a device with a Qualcomm SM8635 Snapdragon 8s Gen 3 chipset, and it just crawls. The UI is very unresponsive, and page load times are terrible.
I have a OnePlus 5T from 2017 with a Snapdragon 835 processor and find that Firefox works perfectly well on it. I also have a device with a Snapdragon 8cx Gen 3 processor and Windows 11 on ARM. Firefox runs smoothly on that too.
The paper notes:
>It is important to note that MP products often contain elevated levels of nucleic acids, constituting ~8% of the dry weight [17], which necessitates consideration when assessing their suitability for human consumption. To address this, a heat treatment process is employed at the end of fermentation that reduces the nucleic acid content in the fermented biomass to below 0.75/100 g, while simultaneously deactivating protease activity and F. venenatum biomass. However, this procedure has been observed to induce cell membrane leakage and a substantial loss of biomass, as evidenced in the Quorn production process [17], which also utilizes F. venenatum as the MP producer. Our experimental trials have encountered similar challenges, achieving a biomass yield of merely ~35%, and observed that heating process increased the relative protein and chitin content (Figure 2D,E), which may be related to the effect of membrane leakage, while the intracellular protein of the FCPD engineered strain was less likely to be lost to the extracellular. Thus, concentrating the fermentation broth to enhance protein and amino acids content in successive steps to produce a highly nutritious water-soluble fertilizer appears to be an effective strategy for adding value to the process (Figure 1).
The challenges of developing economic single cell protein products, that are suitable for human consumption, are described in chapter 3 here:
https://www.researchgate.net/profile/Martin-Hofrichter-2/pub...
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