Nice vision. I like the thought that enzymes are disrupting the chemical industry. But why do you think Solugen's free enzyme is a good idea? Just wondering why ppl won't try free enzymes first before they came to the enzyme immobilization idea?
Hey, inside the article I comment on the mass transfer issue of the immobilized enzyme catalysts coming into contact with all of the actual molecules in the system. Further, historically the cost of enzyme production was high so in theory if it costs $100/kg enzymes are not disposable, especially if you are trying to sell them to people.
According to the Solugen founders they are getting those costs to be 10x lower, which enables them to go with the free enzyme approach so if historically they were $100/kg now they are $10 or if they were $10 now then are $1. A 10x reduction in costs is insane for enzymes and it's the crux of their platform.
I suspect Novozymes is working on similar systems with CRISPR.
They weren't giving me their actual costs because that's somewhat of a secret for them, but
I am also bullish on an enzimatic future for our chemical industry, particularly as carbon externalities get factored in at an accelerated pace. I'm writing "as" rather than "if" because I don't even what to consider living in a world that doesn't.
Thanks for the kind words Francesco. I think overall as costs come down for biocatalysts we can have the best of both worlds when it comes to biomanufacturing and existing chemical engineering infrastructure.
If you do the math on the production rates of 50 g/L/hr in a 30,000 gallon reactor I'm getting about 5,550 kgs per hour in a batch reactor. Pretty good productivity especially if you consider all you need to do is stir it and filter.
- re. "I suspect that CRISPR will enable ambitious start-ups like Solugen to produce a wide array of engineered enzymes at a signicantly lower cost than was once possible due to not needing the high energy inputs." - can I clarify what energy costs you are referring to here? My understanding is that CRISPR is just one means to an engineered microbe - once engineered the energy input is the same vs other routes.
- re. "where their production facilities are located close to their customers and potentially even close to residential areas." this is very exciting, and one of the oft touted benefits of 'decentralized' bio, yet to be realized. Do you have a feeling for how big an impact, collapsing supply chains like this, might have on e.g. Solugen EBITDA....are we talking like 5 percentage points, or like 50????
I think I wasn't a great writer back then...still working on it.
The first part I think I was conflating two points. Use of enzymes reduces energy needs. CRISPR makes editing of microbes to make specific enzymes a lot easier. Easier to produce enzymes = more enzymes available --> less energy.
So decentralization might work, but you need really simple inputs. Any sort of distributed fermentation will likely not work, but for stuff like water softeners or chemicals that are consumed locally I think there is a chance. If you are a consumer of sugar it's better to be closer to your sugar providers and then pass shipping costs to your customers (I think).
Wouldn't expenses increase radially from the primary feedstock of glucose? Meaning that all these touted benefits of their enzymatic technology stem exclusively from their work around one limited set of chemicals placed conveniently close to the only economical and widely available carbon negative feedstock/root chemical (glucose). Lots of the most valuable products stem from pyruvate and beyond, which is around 9 enzymatic steps away from glucose - meaning 9x more enzymes are needed with 9x the diversity and possibly 9x the engineering effort. Lack of that understanding will lead to overinflated projections that these yields and margins will continue into chemicals more distant from glucose, which is not the case.
How do they even source the cofactors needed for this stuff, I don't see much transparency on their end, just touting big yields and huge margins. Something smells fishy to me regarding their environmental claims as well. You can't truly be carbon negative unless you're storing carbon for the ages, and that is not what they're doing - eventually their chemicals (carbon) will be released back into the atmosphere. All up it seems to me that their process is limited to a given radius from glucose, practically carbon neutral, and literally low carbon at best.
Also CRISPR doesn't really help in protein engineering, it helps in metabolic engineering when you want to modify genomes. Protein engineering is primarily a computational endeavour.
Nice vision. I like the thought that enzymes are disrupting the chemical industry. But why do you think Solugen's free enzyme is a good idea? Just wondering why ppl won't try free enzymes first before they came to the enzyme immobilization idea?
Hey, inside the article I comment on the mass transfer issue of the immobilized enzyme catalysts coming into contact with all of the actual molecules in the system. Further, historically the cost of enzyme production was high so in theory if it costs $100/kg enzymes are not disposable, especially if you are trying to sell them to people.
According to the Solugen founders they are getting those costs to be 10x lower, which enables them to go with the free enzyme approach so if historically they were $100/kg now they are $10 or if they were $10 now then are $1. A 10x reduction in costs is insane for enzymes and it's the crux of their platform.
I suspect Novozymes is working on similar systems with CRISPR.
They weren't giving me their actual costs because that's somewhat of a secret for them, but
Thank you for sharing this overview, Tony.
I am also bullish on an enzimatic future for our chemical industry, particularly as carbon externalities get factored in at an accelerated pace. I'm writing "as" rather than "if" because I don't even what to consider living in a world that doesn't.
I'm with you on your "PS" last sentence too.. :)
Thanks for the kind words Francesco. I think overall as costs come down for biocatalysts we can have the best of both worlds when it comes to biomanufacturing and existing chemical engineering infrastructure.
If you do the math on the production rates of 50 g/L/hr in a 30,000 gallon reactor I'm getting about 5,550 kgs per hour in a batch reactor. Pretty good productivity especially if you consider all you need to do is stir it and filter.
wonderful article Tony, many thanks.
- re. "I suspect that CRISPR will enable ambitious start-ups like Solugen to produce a wide array of engineered enzymes at a signicantly lower cost than was once possible due to not needing the high energy inputs." - can I clarify what energy costs you are referring to here? My understanding is that CRISPR is just one means to an engineered microbe - once engineered the energy input is the same vs other routes.
- re. "where their production facilities are located close to their customers and potentially even close to residential areas." this is very exciting, and one of the oft touted benefits of 'decentralized' bio, yet to be realized. Do you have a feeling for how big an impact, collapsing supply chains like this, might have on e.g. Solugen EBITDA....are we talking like 5 percentage points, or like 50????
I think I wasn't a great writer back then...still working on it.
The first part I think I was conflating two points. Use of enzymes reduces energy needs. CRISPR makes editing of microbes to make specific enzymes a lot easier. Easier to produce enzymes = more enzymes available --> less energy.
So decentralization might work, but you need really simple inputs. Any sort of distributed fermentation will likely not work, but for stuff like water softeners or chemicals that are consumed locally I think there is a chance. If you are a consumer of sugar it's better to be closer to your sugar providers and then pass shipping costs to your customers (I think).
Darius in Feedstock land had a good post on this recently: https://feedstockland.substack.com/p/the-basics-of-scale-for-chemical
Nice read.
Wouldn't expenses increase radially from the primary feedstock of glucose? Meaning that all these touted benefits of their enzymatic technology stem exclusively from their work around one limited set of chemicals placed conveniently close to the only economical and widely available carbon negative feedstock/root chemical (glucose). Lots of the most valuable products stem from pyruvate and beyond, which is around 9 enzymatic steps away from glucose - meaning 9x more enzymes are needed with 9x the diversity and possibly 9x the engineering effort. Lack of that understanding will lead to overinflated projections that these yields and margins will continue into chemicals more distant from glucose, which is not the case.
How do they even source the cofactors needed for this stuff, I don't see much transparency on their end, just touting big yields and huge margins. Something smells fishy to me regarding their environmental claims as well. You can't truly be carbon negative unless you're storing carbon for the ages, and that is not what they're doing - eventually their chemicals (carbon) will be released back into the atmosphere. All up it seems to me that their process is limited to a given radius from glucose, practically carbon neutral, and literally low carbon at best.
Also CRISPR doesn't really help in protein engineering, it helps in metabolic engineering when you want to modify genomes. Protein engineering is primarily a computational endeavour.