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It's really nice to see startups working on industrial processes here

AFAIK the main problem with enzymes as catalysts beyond the bench scale is their limited lifetime. How is the half-life of your enzymes at operating conditions? I'm just curious how the process works in real life (so are probably your potential customers).

You say limited lifetime, startups hear recurring revenue ;)

haha yes, we do hear recurring revenue here. Enzymes are indeed fragile relative to metals and have limited lifetimes. However, even metals like palladium leach, sinter, get poisoned, etc. In the current process, many facilities have to continually regenerate their palladium catalysts. The beauty of working with enzymes in the here and now is that we have the tools to continuously optimize them and continuously make them cheaper. We are improving our enzyme lifetimes with each new batch, and we envision being able to release new and improved enzymes to our customers every year

That doesn't answer the question. Even if you're still tweaking things today, what do you expect the useful lifetime of a batch of your enzymes to be, say, a year from now?

more than a month. Best to think of it in terms of H2O2 turnovers per enzyme. Imagine if we made a new enzyme that had 10x faster turnovers but a 5x lower lifetime. Assuming we could still keep up with its oxygen demands, that is a better enzyme despite a lower lifetime.

This sounds awesome and is really way above my head (took crystal chem in college, that's probably my highest chem level).

Some questions:

1. How many kW/kg required to create H2O2 (or another similar, meaningful ratio), and how much do the legacy processes require?

2. When you mention micromanufacturing, how small a scale are we talking about? Would I be able to buy a reactor and make H2O2 in my garage? Or open up a warehouse sized factory in my town?

these are some great questions! kW/kg is really the magic number but very difficult to extract precisely (we do have estimates though from energy balance calculations). A more qualitative way to look at energy cost comparisons is to look at downstream processing after H2O2 is synthesized. Today, they do liquid-liquid extraction, then distillation, then for high purity, they will do up to 5 sequential reverse osmosis operations. Because we do our processing in water rather than alkylated aromatics, we can use ultrapure water from the start...so we don't have to do much downstream processing to get an equivalent H2O2 purity

2. haha micromanufacturing here is relative. Today, an anthraquinone plant consumes the energy of a small city and is multiple football fields in size. They cost >$100m to make. Many of the customers that we talk to use $1-$5m per year of hydrogen peroxide but cannot justify investing in such infrastructure. Our units are modularly designed but will still be close to a football field in size. They address these medium-sized peroxide users that make up the vast majority of H2O2 end-use cases. Today, they pay as much in shipping as they do for the actual hydrogen peroxide. Our units seek to address this. How big is your garage though? Maybe we could make this work!

What is the minimum size you could make it (footprint and capacity)? How small are your laboratory-scale generators today? What would you say about minimum size while remaining economically viable, not simply theoretical?

Seems the process is simplified in terms of stages over the existing pipelines,lending itself to smaller scales.

Well our current facility takes up ca 2000 square feet and has sufficient capacity for our new consumer product launch, it really depends on what you want to do with the peroxide. If you want to compete on price against the current process though, it still has to be a lot bigger than our pilot facility.

It sounds like great stuff, but here's an ad copy nit:

  "Bioperoxide, the hero ingredient of Ode to Clean"

Using "hero ingredient" instead of "active ingredient" seems like getting a little too enthusiastic on the marketing. (Not to mention using two made-up terms in the same sentence...)

More generally, I'm looking for a page that explains the science behind the safety and effectiveness (for the end user) in a more technical way, and not finding them. "No toxins" and "made from plants" doesn't seem like enough of an explanation.

The ad copy for household cleaners hardly ever explains much of anything about the science, but why not do it better?

You say 'explode' three times in this post, and once you state that the reason for peroxide plant explosions is the petrol side of things.

Would you elaborate on that? I was under the impression that ordinary peroxide from any source can cause explosions. A quick web search for 'peroxide explosion' seemingly confirms that.

But, I'm no chemist. You tell me, please!

No worries, I will do my best! Yes, peroxide from any source can cause explosions, but usually only at high concentrations in water. At low concentrations (below 8%) metal contaminants, especially precious metals like platinum and palladium, can cause explosions.

During manufacturing, hydrogen peroxide is synthesized at low concentrations in the anthraquinone process (below 8%). However, it is manufactured in a highly explosive alkylated aromatic solvent and in the presence of a palladium catalyst. Both hydrogen and oxygen are used, which when combined will explode quite easily. The current manufacturing process goes to great lengths to keep the hydrogen and oxygen in separate chambers, but inevitably something goes awry. What is a pretty common problem is after liquid-liquid extraction, there is some residual hydrogen peroxide left in the aromatic solvent that makes its way into the hydrogenation chamber. In this scenario, you have hydrogen gas, palladium metal, a flammable solvent...and hydrogen peroxide all in the same vessel...which is a bomb :(

Our process doesn't use metals or a flammable solvent. We replaced them with enzymes and water.

I assume your process creates a relatively dilute aqueous solution of hydrogen peroxide? So you'd still need to concentrate it, I assume by distillation? That's a risky process. Will you do that yourself?

Excellent work gchakr and seanhunt1! I love that you are thinking 3M big ;)

I'd also like to hear more about the CRISPR enzyme engineering process. How do you actually research, design, and manufacture at scale. And no, you don't have to divulge any secret sauce. Just point me to some open science resources ;)

If your modified enzyme based chemical manufacturing process is truly as revolutionary as it seems. Then I'd like to see your marketing reflect that. Think of a single cartoon image or logo design that can communicate to the public at a glance the idea that you are now using DNA to deliver 100X efficiencies in chemistry. Best of luck!

Living factories of the future

https://www.nature.com/nature/journal/v531/n7594/full/531401...

Is there any expectation that you will be making hydrogen peroxide for sale in the usual brown bottle, like you can get at pharmacies, etc? If so, what kind of price point would you expect.

As someone who uses a lot of peroxide and prefers nontoxic cleaners, the product sounds great to me, but the cost seems on the high side. I am thinking that as a minimum, you should have a blog or FAQ or something that outlines ...hidden costs of traditional peroxide? Like show the externalities of those processes and place a dollar amount on them. This might be a means to make it clear that the cost difference isn't really as big as it might sound, if that makes sense.

Another question after looking over your site: could you start a side business looking into microorganism-based carbon sequestration? I know this is something that other people are looking at, but you seem to have a lot of experience in chemistry and bioengineering, and you specifically mentioned CO₂ capture as an incidental benefit of your production process.

If you had microorganisms that captured orders of magnitude more carbon from the atmosphere as part of their metabolism (or indeed just other enzymes that catalyzed other chemical processes that had that effect), maybe people would want to pay you to breed a lot of these organisms.

I never expected to see any substantial non IT company here, but looks like it is!

I forward you my encouragements.

Thank you! Building a chemical company is no small feat, but being able to de-risk the technology scale-up at every step is absolutely critical to success.

Really happy for Solugen's success and what this means for other biotechs seeking to augment traditional petromethods with enzymatic ones.

Can you help us better understand how you use CRISPR/Cas9 to mutate the protein? Your enzyme is proprietary, sounds like human protein, but mutated in certain positions prob to increase rate, but how do you use Cas9? I assume like other biotechs you purify this single protein using either E. coli or yeast with protein on plasmid. So why use Cas9 instead of site-directed mutagenesis?

So, without going into too much detail the use of crispr/cas9 in our studies is even simpler than driving protein mutagenesis. We have been exploring CRISPRi has a mechanism to inhibit key promoter repressors of our gene of interest. We've found that we can affect affect specific protein abundances by changing the rates of both RNA synthesis and protein degradation, based on the two cross-kingdom control mechanisms CRISPRi and the N-end rule for protein stability.

Hi there. There is a good potential market for you among floatation centre owners / spas. The use of Hydrogen Peroxide and UV in combination as a water sanitising technology is very popular, and giving the owners of float centres and spas the ability to say they use plant based peroxide produced using enzymes would be a powerful marketing message to their customers.

Sounds interesting - how much water is produced in the process, or is it only synthesizing H2O2? Also, if your catalyst is regenerating from plant sugars, do you lose some of the catalyst when you extract the H2O2, or is some consumed by side reactions?

Our process doesn't produce water. The H2 comes from starch and the O2 is taken from the air. Catalysts are self-regenerating, although enzymes do naturally degrade over time.

What happens to those "degraded" catalysts? I guess you do have to remove them and dispose of them somehow? And you must have a lot of them, since you only use the H2 from starch and all the rest is "catalyst", as you seem to suggest in your introductory blurb.

In short, saying that "the only output is H2O2" is... weird. You may prefer not to call them outputs, but what are the waste products that are produced, how much of them, and what happens to them?

This is really exciting! I hope it's just the beginning of a green chemical revolution!

There have been many false starts in the green chemicals field. I think the most prudent way to make this an actual revolution is to make money;)

That's really interesting! What's the energy source that drives this reaction? (Where does the energy that becomes the additional chemical potential energy in the peroxide come from? Is it from oxidizing the plant sugars?)

Great question! The reaction is actually thermodynamically downhill and spontaneous (delta G less than zero). The current manufacturing processes use palladium catalysts that do have an activation barrier that requires heat. Enzymes are much more efficient and can catalyze this reaction even below room temperature.

That's counterintuitive to me because I know peroxides have quite a bit of potential energy (for example, because of their use in fuels). Are you starting from sugars that have even more?

yep, sugars have more internal energy than peroxide (you can just add up all the bond enthalpies for a quick estimate). Peroxide is used in fuels because 1.) it is much easier to activate than sugars because it is thermodynamically metastable and 2.) it is an oxidizer. Oxidizers help accelerate the release of internal energy from energy-dense fuels (e.g. kerosene...or even sugar). Another way to look at this is reduced vs oxidized. O2 is the most (stable) oxidized form of oxygen while H2O is a reduced form of oxygen. H2O2 is intermediate. Hexane is a very reduced C6 compound (high internal energy) whereas 6 CO2 molecules are the most oxidized (low internal energy). glucose is intermediate between hexane and 6 CO2 molecules but closer to hexane in terms of how reduced it is. Glucose is quite energy dense and it is for this reason that it is used by plants to store energy from sunlight.

"Ode to Clean is the world's first cleaner that’s derived entirely from plants- even the wipes themselves are made of plants." [1] This claim is obviously false. There are been many %100 plant based cleaning products in the past.

[1] https://odetoclean.com/products/the-ode-to-clean-kit

Gaurab, great talking with you in the early days and exciting to see you launch!

What are some challenges in reactor design? I would imagine that extracting the H2O2 would be a tricky so it doesn't kill the enzymatic process.

Hey! We're really excited too. The biggest challenge with reactor design is getting excellent oxygen mass transfer (called the Kla "Kay el aye"). Typical fermentation reactors see a background dissolved oxygen concentration of around 8 ppm. The enzymes in the cell can see much lower concentrations, around 1 or 2. Our reactor delivers 450 ppm of dissolved oxygen to nearly every point in the reactor, greatly boosting the kinetics (and efficiency) while also mitigating the effects of H2O2 inhibition on the enzyme. Second, our reactor is also the separator (we use molecular weight cutoff membranes) so that we can continuously remove the peroxide as we make it while retaining the enzyme. The last challenge is materials. Metals decompose hydrogen peroxide and also leach out slowly into the water, lowering purity and reducing the shelf life. Thus, we are using a lined reactor. For non-peroxide producing enzymes, we can design a 316L steel version of our reactor for interested customers that is less expensive.

Interesting stuff!

What sort of temperatures and pressures do you have in the reactor?

[Edit: Temperature is around human body temp, of course. I assume it's pressurised in order to get the O2 concentration way up there. So a little north of 800 psi, if my math checks out?]

Do you need to care about hydrogen embrittlement?

Do you have any numbers on CAPEX per production rate as compared to traditional production?

Thanks! We are finding that sub-ambient temperatures are working the best (ca. 10-20 celsius). For improving reaction rates, elevating pressure is much less energy intensive than elevating temperatures, and is extremely useful for improving dissolved oxygen concentrations. Currently, we use class 150 lb components and operate around 100 psig but are looking to test out higher pressures in the future for even better efficiency. Your match checks out, but we also use a pressure swing adsorption system to send in >95% O2 rather than 21% air. We also use a proprietary sparging unit to get super-fine gas bubbles with low rise velocities. Enzymes appear quite resilient to high pressures vs. high temperatures. I suppose this is because water is largely incompressible so it does not affect the enzyme geometry even at high pressures. Yes, we do need to care about hydrogen embrittlement (always a problem) but hydrogen processing is tried and true in the industry and we operate at pretty low temperatures. CAPEX-wise, we are around 10x lower (at equal production rates) because we combine several unit operations into a single unit and we have eliminated the need for a liquid-liquid extractor. Around 50% of the CAPEX costs and >50% of the energy costs with the current anthraquinone process are related to distillation. Because we are much more efficient, we are hoping to have smaller units on site with customers that will eliminate the need for distillation all together, which removes a large portion of both the CAPEX and operating costs associated with the traditional process

Thank you for the long answer!

Yeah, few biological processes care about the effect of pressure other than the changes caused in solubilities etc. The physics of the sparging process is very interesting. Do you also do countercurrent (downwards) flow of the water in the sparging unit? (Settling velocities of microdroplets is a subject close to my heart.) I guess anti-foaming is also a big concern there.

A word of caution on pressure classes: in some conservative industries (e.g. oil and gas) they won't let you get away with using piping components rated at some pressure class as pressure vessels at the same pressure class without additional certification. Say, if you were using a piece of large diameter 150 lb rated pipe with flanges at each end as your reactor body. Certification as a pressure vessel is more exhaustive/expensive than certification for piping components.

Nice trick going with the PSA unit instead of accepting the large O2 partial pressure penalty. It sounds like you guys run a tight ship, all the best of luck!

Thanks so much for this advice, very helpful!

As an ethical vegan who tries to avoid tropical plant materials, would you mind specifying if your plant inputs are from the US or from a 3rd world country?

Just as a note, your website has no favicon, which looks really unnatural in Chrome.

Aside from that, it is great seeing such a cool biotech project going straight to the consumer market!

Ahh yes! We are new to the favicon game, thank you for pointing this out for us!

We should have the molecular structure of H2O2 as our favicon

Not an electron density map?

Great to see this innovation. Good luck with your venture. I'm very hopeful that we can replace many other industrial toxic processes with clean bio alternatives

Thanks, this is Solugen's biggest goal!

Where does the H2 come from? Electrolysis? Fossil fuels?

I don't know about their source, but on a global basis roughly 5% of H2 comes from electrolysis (any electricity source) while 95% comes from natural gas via steam methane reforming (chemical conversion using CH4, O2 and H2O to make H2 and CO2).

Yep, this is correct! It largely depends on the country's electricity costs vs. access to natural gas. In some instances, rather than methane steam reforming, dry methane reforming is also used. Currently, almost all large-scale peroxide plants using the current technology (the anthraquinone process) are built next to natural gas reforming plants.

Currently, the H2 comes from waterplitting that occurs in the photosystem II of plant cells. We are now working on a system where the H2 comes from bulk water electrolysis, which is now more efficient than plant cells

Are there any advantages to an enzymatic approach to chemical production vs fermentation?

Yes! Enzymatic chemical production supplanting traditional fermentation is why Solugen exists. Historically, enzymatic production is used in only 3% of all chemical production processes. However, with CRISPR/Cas9 and the second wave of biotech, enzymes are becoming cheaper to engineer and even cheaper to mass-produce. People have tried fermentation to biofuels in the past, but it didn't work. Cells are really really good at making proteins, like enzymes, but they suck at making just a single chemical product. Downstream separations become a nightmare. We think it better that fermentation should be exclusively used to make enzymes and then those enzymes should be used to do single-chemical manufacturing. Our core technology revolves around designing and providing customers with the perfect scaled reactors for their enzymatic technologies. Fermentation reactors severely limit the capabilities of enzymes, and the reactors in the petrochemical industry are also ill-suited for enzyme manufacturing. We like to call our work "enzyme-reactor" fit!

Is your technique economically viable on its own or does it require subsidies?

At scale, our technique is economically viable on its own (but subsidies would always be nice I suppose). Currently though, we are on a pilot scale so we cannot yet compete on volume, hence our gtm strategy of differentiated hydrogen peroxide products.

Yours is one of the more intriguing startups I've seen. My background is in software and developer advocacy - my job is to figure out how to convince people of true ideas.

I'd like to offer some unconventional advice.

Subsidies hurt the people who take them the most, because they destroy self-confidence (belief in your own efficacy) and undermine self-esteem (knowledge that you have earned your achievements). I'm glad to hear you do not need them.

You have rigorously applied your mind to create an objective good - a new chemical process which will promote human flourishing.

Strike all mentions of the petroleum industry and of toxins. There are two main problems with these.

First, they are not differentiating your product on its essential value, which means every moment spent making the negative case for them is lost to making the positive case for your product.

Second, you are being dishonest and are appealing to emotion. Dishonest because, with doctorates in oncology and chemical engineering, you know words like "toxins" are deeply nuanced; and even in your post to HN, you attack petroleum in one sentence, then mention your products application to plastics in the next. Appealing to emotion because you surely know the public's fear of chemicals is not based in reason.

Next, strike mentions about the expense of peroxides, their dangers, and explosions at peroxide plants. These are not differentiating, unless your go-to-market strategy is fundamentally based on licensing the technology to existing peroxide producers. As a consumer, I perceive peroxides to be so cheap as to be beneath notice - if you mean they are expensive in industrial applications, just talk about that directly. I don't know anything about how to judge the impurities in peroxide - just talk about the value of why purity matters, which I think you do in point 3 (though I'm not sure). And industrial accidents happen - unless your claim is that you are going to put the entire peroxide industry out of business, those explosions are going to continue to happen - instead, talk about why the stability of your product is a value.

Strike the Ode to Clean product, unless it connects with your core go-to-market strategy. It is an incredibly expensive product. You can probably make a lot of money because people make emotional purchasing decisions, but it is also a distraction from the phenomenal applications you mention in your HN post.

Does this lay the foundation for carbon neutral rocket fuel?

haha we talked to some rocket companies, and it isn't an area we plan to enter soon, but technically yes we could! Even with the current anthraquinone process, hydrogen peroxide is still a much "greener" monopropellant than hydrazine, although I believe monopropellants in general are not as popular nowadays.

Congrats Gaurab and Sean! Excited to see your progress.

thanks so much!

In your advertising material for ode-to-clean you imply that your H2O2 is somehow fundamentally different in the end product to H2O2 manufactured in other ways.

You describe it as being "toxin free", and yet also have this paragraph, "the chemicals in our cleaning products, like hydrogen peroxide, are dangerous, expensive, and come with an enormous carbon footprint" on your "bioperoxide" page.

Yet here you describe that you're manufacturing that"dangerous, expensive" hydrogen peroxide.

Isn't it very misleading to sell a product based on differentiating yourself as "non-toxic" and "natural" when chemically it's the same to the end-user, just the process that is different?

I think in that sentence, "hydrogen peroxide" is an example of "cleaning products", not of "chemicals in our cleaning products". Could be clearer.

agreed! We are working on this one, thanks!

thanks, I think we need to do a better job at differentiating between hydrogen peroxide the molecule vs. the hydrogen peroxide production process. We'll update this section today so that it hopefully is more clear. Here is what I am thinking:

1.) Hydrogen peroxide the molecule is a beautiful molecule and all hydrogen peroxide molecules are the same. Hydrogen peroxide is safe and decomposes into just water and oxygen so it doesn't leave behind solid residue or pose an inhalation hazard. The differences arise in terms of purity. Today on the market, you can buy technical grade, food grade, five different semiconductor grades, and rocket grade. Bioperoxide has semiconductor grade purity. Most other hydrogen peroxide products on the market (especially in the consumer space) are made using cheap technical grade peroxide that has heavy metal and alkylated aromatic contaminants. This is what we mean by "toxin free"

2.) Hydrogen peroxide the process is what we are referring to in "the chemicals in our cleaning products, like hydrogen peroxide, are dangerous, expensive, and come with an enormous carbon footprint." Our manufacturing process is not dangerous since we are not mixing hydrogen and oxygen in an aromatic solvent, is cheaper, and our Houston facility is operating on wind energy.

Please let me know if this makes more sense, thanks!

Launch HN: Solugen (YC W17) – Plant Sugars to Hydrogen Peroxide