Back in September 2015, we reported that Amyris inked a multi-year agreement with the US Defense Advance Research Projects Agency, the famed DARPA that gave us everything from kevlar to the Global Positioning System and the Internet — the goal in this $35M agreement with the Biological Technologies Office was to create new research and development tools and technologies — compressing the time to market for any new molecule by at least 10-fold in both time and cost.
The story expanded this week when we heard from Amyris that it had completed strain engineering and optimization to 26 key metabolic precursors across multiple organisms – including many different pathways beyond terpenoids allows Amyris to develop an industrial-scale fermentation process for virtually any biological molecule.
In addition to the expansion of the range of metabolic precursors, Amyris has revealed that it has now expanded its high-throughput yeast strain construction and testing pipeline to several other industrially-relevant organisms.
The DARPA was called Living Foundries.
The molecules were anticipated to include chemical building blocks for accessing radical new materials that are impossible to create with traditional petroleum-based feedstocks.
These advancements have the cumulative effect of drastically reducing the R&D costs and timelines for developing a commercial process for any biological target, irrespective of the final application of the molecule. This is empowering Amyris with additional resources to develop next-generation capabilities to further advance its competitive position and accelerate its capabilities to produce go-to-market sustainable supply solutions at industrial scale for its partners.
“The DARPA-funded TIA has allowed us to continue our pioneering efforts at applying automation, next-generation analytics, and machine learning algorithms to find biological solutions to the bio-manufacturing sector,” said John Melo, Amyris President and CEO. “Amyris has always been at the forefront of utilizing big-data analytics and cutting-edge tools in the biotechnology sector, and our recent R&D results continue to pave the way toward expanding our footprint in multiple markets where fermentation-derived products offer our partners and consumers a sustainable, scalable source of supply.”
The new sweetener
Not completely unrelated to Amyris’ new-found chops in strain construction is the news that Amyris has “made significant progress” in the development of its healthy sweetener product technology and expects industrial production to occur in 2018. We reported on this earlier this week in our sister publication, Nuu — here.
Amyris is making a No Compromise sweetener and says it is “on track to be the low cost leader at industrial scale production” with a natural-like sweetener with very low calories that is sustainably sourced. Amyris’s target is to sell the world’s leading sweetener at a lower cost than sugar without any negative taste. Consumers love soda but hate sugar — Amyris wants to make soda taste the same and be healthy. The company expects this product opportunity in partnership with its partner to deliver over $100 million in annual revenue by 2020.
Beyond conventional sugar as a starting point
One of the things that the announcement portends is a step beyond conventional sugars as a feedstock in a conventional way. Note that Amyris will be selling at a lower cost than sugar.— and that rules out starting from conventional sugars in a conventional way.
One possibility? The company could be targeting something like xylitol — which is a C5 sugar and used as sweetener. Or, sorbitol — which is a C6 sugar alcohol that the human body metabolizes more slowly than conventional sugars. A patent search has not yet revealed any particular targets coming out of Fortress Amyris.
Polyalcohols are often used in foods like gum or even toothpaste because they offer the sweet taste without the cavities. However, they aren’t cheap as they can’t be found easily in nature and when produced industrially, they need very specific and controlled environments making it a pain for wide scale production.
We reported in Nuu last December that the Institute of Chemical Research of Catalonia and the Swiss Federal Institute of Technology researchers found a way to get polyalcohol sweeteners like mannitol or ribitol from cheap renewable sources like glucose. By being able to reorganize sugar atoms, researchers found a way to get the valuable polyalcohols from regular sugar easily and more affordably, bringing a smile to candy, gum and toothpaste manufacturers around the world.
Or, the company is proceeding from a novel sugar precursor where it can generate a higher yield. such as starting from unprocessed cane juice, which has the molasses still in the mix (in conventional white sugar refining, all the molasses is removed).
So, there are questions to be answered and we are standing by on that.
“Our focus on supplying the lowest cost, best performing products into Health & Nutrition and Personal Care markets by partnering with the leading brands has very strong momentum,” said John Melo Amyris President & CEO. “Our efforts to give the consumer sustainably sourced, best performing products without dangerous ingredients is really starting to payoff. We believe we have the leading market position for sustainable, healthy sweeteners and we are very excited about helping the world transition away from unhealthy sugars and accelerate the use of healthy sweeteners by providing the consumer a better taste experience and our partners better economics.”
The Race for a Next-Gen Sweetener
The race for the next big sweet-tooth satisfier has been heating up significantly.
We reported in April that Cargill and Evolva inked a major collaboration pact for the production and commercialization of EverSweet, the next-generation stevia sweetener. This product is on track for a 2018 launch, securing its first-mover advantage.
Over the next three years, principally in 2018 and 2019, Evolva expects to invest an estimated USD 60 million in the combined fermentation and bioprocessing facilities for EverSweet and its other products. The recent CHF 30 million equity commitment from Yorkville serves as a foundation for this investment and Evolva expects to secure an additional project financing package of around CHF 30 million by end 2017, which will enable full execution of the plans.
We reported in Nuu in February that MIT spin-out Manus Bio is using multivariate modular metabolic engineering to design microbial pathways that produce larger volumes of commercially interesting compounds.
Using MMME, the company has developed a fermentation-based process to produce Rebaudioside M with greater than 95% product purity. Currently, the alternative sweetener is derived in low yields from the stevia plant.
“Slapping genes together to make a product is fine, but this doesn’t give you a platform for producing something economically,” Stephanopoulos says. “There’s a big jump between making a few milligrams of a compound and a few grams, which is what you need to make it commercially viable.”
MMME involves using enzymes to “cut the linear pathway into a network of separate, distinct modules that can be more easily controlled and modified.”
Manus is also working on developing a route to nootkatone, a grapefruit extract that is a natural insect repellent. Traditional nootkatone production methods cost several thousand dollars per kilogram.
We also reported last October that S2G BioChem had entered into a license and collaboration agreement with Mondelēz International — a leader in biscuits, chocolate, gum, candy and powdered beverages — to help commercialize a sustainably-sourced supply of the food ingredient xylitol using a proprietary co-production technology.
Commercial-scale production of the sustainably-sourced food ingredient xylitol is expected to begin in 2018. Mondelēz owns billion-dollar brands such as Cadbury, Nabisco, Oreo, Trident and Dentyne.
We also reported last November that DSM asked Europe’s food safety regulators to approve the use of stevia produced using fermentation. The popular sweetener has already been okayed for consumption in Europe, although the regulation stipulates it be produced via water extraction of the Stevia rebaudiana plant followed purification and recrystallization. DSM’s process uses fermentation with a genetically engineered yeast to steviol glycoside.
The Bottom Line
New targets at new speeds — that’s what DARPA is trying to change. Clearly they’re looking not only for next-generation materials that have advanced properties with potential military applications — they’re looking to endow friendlies with the capability to make them faster. That not only changes the economics; it changes the potential that science can respond more effectively to the shortages, disruptions, and theater-level strategic opportunities that conflict brings.
The connection between DARPA and sugar might not be obvious. Of course, not everyone saw the point of demonstrating an internet, either, back in the days of ARPA.
The connection here is that a commercially-relevant challenge like a sugar alternative — and the race to get to market at the lowest cost — presents an opportunity to develop tools that DARPA will need for a host of molecules that no one knows how to make affordably and commercially — if we know how to make them at all.
Stronger materials, more flexible materials, materials that think, materials that respond to conditions — whether it is lightweighting military vehicles or providing better protection to military personnel, or just finding things that explode better — DARPA has a real stake in developing manufacturing and, for military applications, speed has an incredible premium.
DARPA shares a passion for pace with every company chasing a new sweetener — and also with every investor who would like industrial molecules to come out at scale, faster, from the new industrialists like Amyris. The collaborations are getting mighty interesting.