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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 (AMRS)
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
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.
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
“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
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
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
Jim Lane is editor and publisher of Biofuels Digest where this
was originally published.
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