Can industrial biotech merge mass production and haute couture into a new, tailored yet industrial system for products and materials?
Companies like Joule may have the answers.
A long time ago there was a children’s television show called Romper Room, with two recurring characters called Mr. Doo-Bee and Mr. Don’t-Bee – oversized bees that helpfully offered instruction along the lines of “don’t BEE toy selfish,” or “do BEE good boys and girls.”
In biofuels, most technology development is of the Doo-Bee variety: “Do BEE a good jatropha bush and produce a higher yield of oil for me please.”
But some of the most interesting work being done today at Joule Unlimited is of the “Don’t Bee” type: progressively knocking out characteristics and pathways that create limitations on biofuels production: “Don’t BEE a naughty e.coli and make too much biomass when you could be making pyruvate.”
Imagine, for a moment, if your own human inhibitors were not always at work – inhibitors that make you sleepy, feel full after a meal, tired after a workout, blink in the presence of strong light, or make you feel stressed out after reading about the Grocery Manufacturers Association.
The Joule backstory
Now, Joule is a mysterious company, which is to say that most of their appearances in the press relate to various additions to their board of directors and team (impressive) and various venture capital rounds (like Arabian sheikhs). There hasn’t been a lengthy discussion by the company on many occasions, of the technology itself.
What we know is that it is a system, not an organism – a small-scale unit which can be replicated almost infinitely, which provides a medium for an engineered microbe to fix CO2, and draw in brackish water and other nutrients, use those ingredients to overproduce a target fuel or chemical, sweat the fuel – which is then separated from the growth media, and delivered through a channel where it is collected for distribution.
The Joule system, to date, looks remarkably like a solar panel – which in many ways, it is, because the organism is photosynthetic – except that it is a bio-solar system.
At the heart of the system, of course, are the magic bugs themselves – or rather, the system by which Joule creates a host of magic bugs. At the heart of that organism is metabolic engineering – that is, manipulating the metabolic pathways by which an organism creates all the chemicals it needs to grow and survive from base inputs like CO2 and water.
Moving towards new platform microbes
As Joule scientists observed in a recent patent filing, “Photosynthesis, as naturally evolved, is an extremely complex system with numerous and poorly understood feedback loops, control mechanisms, and process inefficiencies…Existing photoautotrophic organisms (i.e., plants, algae, and photosynthetic bacteria) are poorly suited for industrial bioprocessing and have therefore not demonstrated commercial viability for this purpose. Such organisms have slow doubling time (3-72 hrs) compared to industrialized heterotrophic organisms such as Escherichia coli (20 minutes), reflective of low total productivities. In addition, techniques for genetic manipulation (knockout, over-expression of transgenes via integration or episomic plasmid propagation) are inefficient, time-consuming, laborious, or non-existent.”
Well, certainly companies like Solazyme and Sapphire Energy are addressing the lack of techniques for genetic manipulation in algae, in some of their applied research, but the point is generally true.
So much so that Joule has widened its proposed playing field, of late: “In additional embodiments, the engineered cell provided by the invention comprises an the cell is selected from eukaryotic plants, algae, cyanobacteria, green-sulfur bacteria, green non-sulfur bacteria, purple sulfur bacteria, purple non-sulfur bacteria, extremophiles, yeast, fungi, engineered organisms thereof, and synthetic organisms.
In terms of Mr. Don’t-Bee activities – which is to say, removing inhibitors that cause organisms to slow or stop production of target fuels and chemicals, or removing complete metabolic pathways that produce materials of low interest – well, reading Joule patent apps is as good a way as any to check in on the state of the art.
And, watching Joule as it considers the problem of how to make the organism secrete the target fuel or chemical.
Critical point, that one. Usually, as in the case of annual crops, we bioprocess the organism to fraction out the products we need – killing off the organism in the process.
Great to get all that product – corn syrup, corn oil, ethanol or what have you. But in the process you lose the organism and all the energy that went into creating it. Of course, there are perennial bushes like jatropha where the organism is saved – but the time to grow the tree itself is an inhibiting factor .
In the Joule universe, you milk the organism, rather than slaughter it. Joule makes cows, rather than bulls for the beef market.
Joule’s approach, then, is reductive. By simplifying the organism to address inefficiencies that natural evolution introduced, you optimize the system.
As its scientists explained in a recent filing “In some aspects, ethanol production is optimized by channeling carbon away from glycogen and toward pyruvate, etc. during light exposure. Normally glycogen is formed in the light and it is consumed for reducing power in the dark. In one embodiment, glycogen-synthesis genes are attenuated or knocked out and in other embodiments, glycolytic genes are made constitutive. In other aspects, certain fermentative pathways, such as those leading to acetate, lactate, succinate, etc., if present, are eliminated.”
What Joule’s organisms can make
To date, Joule has reported making a wide variety of sugars, alcohols, fatty acids and hydrocarbons, with carbon chains from 2 to 34 carbon atoms in length.
Joule reports: “Such products range from alcohols such as ethanol, propanol, isopropanol, butanol, fatty alcohols, fatty acid esters, wax esters; hydrocarbons and alkanes such as propane, octane, diesel, JP8; polymers such as terephthalate, 1,3-propanediol, 1,4-butanediol, polyols, PHA, PHB, acrylate, adipic acid, .epsilon.-caprolactone, isoprene, caprolactam, rubber; commodity chemicals such as lactate, DHA, 3-hydroxypropionate, .gamma.-valerolactone, lysine, serine, aspartate, aspartic acid, sorbitol, ascorbate, ascorbic acid, isopentenol, lanosterol, omega-3 DHA, lycopene, itaconate, 1,3-butadiene, ethylene, propylene, succinate, citrate, citric acid, glutamate, malate, HPA, lactic acid, THF, gamma butyrolactone, pyrrolidones, hydroxybutyrate, glutamic acid, levulinic acid, acrylic acid, malonic acid; specialty chemicals such as carotenoids, isoprenoids, itaconic acid; pharmaceuticals and pharmaceutical intermediates such as 7-ADCA/cephalosporin, erythromycin, polyketides, statins, paclitaxel, docetaxel, terpenes, peptides, steroids, omega fatty acids and other such suitable products of interest.”
The bottom line
Well, the capability to make something, and the capability to make it, affordably at scale – those are two vastly different things. But Joule’s ambitions are clear – it is not making an engineered magic bug that can spit out a fashionably high-priced product. It is not, to use an analogy, making a silkworm. Rather, it is making a loom – a system that can be programmed to produce a huge array of products by simplifying, and speeding up the industrial process.
The loom and the steam engine – well, those were the foundational machines of the Industrial Revolution. Suggesting that Joule should be seen as the maker of a foundational machine, that happens to create fashionably-priced chemicals and fuels, rather than strictly as a fuels or chemicals producer.
It’s the latest trend in biofuels – moving away from the integrated biorefinery, that fractions a given biomass into a host of useful mass-produced products, but always limited by the properties of that given biomass. Moving towards the integrated bioengine, that has relatively unlimited abilities to tailor and target – moving organisms into its fermenters or biosolar panels, like replacing the punchcards that drove Jacquard looms.
A powerful platform indeed.
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