Fermentation Frontiers: Top 10 Trendlines in industrial biotech fermentation


The most visible advanced industrial fermentation target for a number of years has been cellulosic ethanol, but the targets are diversifying and cellulosics themselves are shifting gears from process to feedstocks. There’s a fervent ferment in fermentation these days.  Today, we go through the  Top 10 Trendlines that have emerged in the headlines.

#1: The secret is out about Genomatica’s 1,3 butylene glycol

We reported this summer the biggest news: Genomatica’s Bio-BG butylene glycol using their new GENO BG process, which makes a naturally sourced 1,3 butylene glycol. Production already has started in 85,000 liter fermentation tanks at EW Biotech in Leuna, Germany.

While the GENO BG process was developed in stealth mode, the secret is out and its advancement has been super-fast, even beating out Genomatica’s GENO BDO process which quickly hit milestones on plant performance guarantees and worldwide production.

We thought GENO BDO (1,4 butanediol) was pretty cool, especially when it was scaled up so quickly, so why do we think GENO BG is too? Genomatica’s new biobased process technology makes a naturally sourced butylene glycol that can replace the existing fossil fuel derived acetaldehyde that is toxic, an irritant and a carcinogen. Not good considering butylene glycol is used in many cosmetics to improve moisture retention and as a carrier for plant extracts, and many consumers are now demanding healthier products.

Genomatica’s innovation now offers personal care companies a more naturally derived, nontoxic option with its plant based ingredients. Even better, Genomatica’s version is a distinctively pure product and a simpler process design compared to fossil fuel-derived, chemistry-based processes, making it a great choice for large scale deployment.

#2: Cargill, Evolva to bring next-gen sweetener to scale

In April, we reported 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.

#3: Amyris, DARPA and Living Foundries

Back in September 2015, we reported that Amyris inked a multi-year agreement with the US Defense Advance Research Projects Agency 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 summer 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 project 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.

#4: Epic cellulosic projection shift at EPA

Last week, we reported on Jeremy Martin’s incisive analysis of EPA’s doings. We reported on his clear demonstration of how the Environmental Protection Agency shifted gears in mid-June by scrapping the cellulosic biofuel target based on corn kernel technology that has been successfully ramping up and instead focusing on the slow-to-commercialization large-scale facilities that haven’t performed as well as they should have. The earlier methodology proposed pre-June 23 would have increased the cellulosic biofuel mandate in 2018 from 2017 in line with this expansion in corn kernel production but instead was cut June 23 by more than 150 million gallons, sending negative signals to investors in advanced biofuels.

#5: New applications

In July, we reported that KnipBio completed the last phase in producing its new aquaculture feed, KnipBio Feed and is now looking to partner with biofuel industry leaders to get to commercial scale fermentation. As reported in Biofuels Digest before, KnipBio developed a series of naturally occurring microbes that convert low-cost feedstock into premium, nutritious, single-cell proteins laden with pigment-enhancing carotenoids to produce healthier, more vibrant fish.

National Research Council of Canada was involved in the project. The goal for their program was to get it from lab to pilot-size production, and their next step is to continue field trials of the fish feed and demonstrate its improving . They expect to get it to commercial-scale manufacturing sooner than anticipated, though no specific date was given.

#6 Effective combinations are the ticket: QCCP

Just before the Labor Day break, we reported that QCCP CEO Delayne Johnson said that if all of the ethanol plants in the US switched to Enogen corn and used Cellerate technology like the QCCP does, then the Renewable Fuel Standard’s cellulosic ethanol mandate could be reached without grinding any additional corn. Last year, cellulosic ethanol production only reached 176 million gallons compared to the 230 million gallons mandated by the RFS and the 238 million gallons set for 2018, lowered from the planned 311 million gallons.

A strong advance on that front just appeared on the radar last week, in Galva, home of Quad County Corn Processors. In April of 2017 Taurus Energy, Lallemand Biofuels & Distilled Spirits, Syngenta and initiated a trial of Taurus Energy’s xylose/C6 co-fermenting yeast XyloFerm in the Cellerate process to evaluate performance at large scale. The trial has concluded and results confirm that XyloFerm can successfully convert C5 and C6 sugars to ethanol in the full scale industrial process. We note that for the foreseeable future work will be performed at lab scale and/or pilot scale due to scheduling restrictions at Quad County Corn Processors.

Last August we reported that Quad County Corn Processors reported a 26 percent increase in ethanol production after a recently-completed trial. The trial consisted of a combination of Cellerate process technology and Enogen corn. Brotherson said this dramatic increase was achieved by realizing an additional 6 percent yield per bushel from converting kernel fiber into cellulosic ethanol, plus a 20 percent throughput increase by combining Cellerate with Enogen.

#7: There’s hot tech right inside the landfill

Usually, we report on landfill waste as a feedstock, but we reported in August that a new research paper in mSphere identified the enzymes which degrade natural materials such as paper and clothing in landfill sites.  Scientists have been searching for a number of years for the most effective enzymes which break down the cellulose and lignin within the residual natural fibers. The obvious place to search has been in the rumen of sheep and cows, who eat grasses, and the guts of also other plant eaters such as elephants and termites.

Surprisingly perhaps, landfill sites share many of the same characteristics as the digestive systems of these animals: they are dark, anoxic or un-oxygenated spaces, with a high content of cellulose. It was therefore to landfill sites, which are artificially created ‘systems’, that this group of scientists turned to find new plant-degrading enzymes.

#8: Feedstock advances

Looking at roadsides 

Last month, we reported that Urbana researchers are implementing a pilot program based on a three-year study that showed nearly $2 million in energy could be recovered by harvesting more than 100,000 acres of unpaved public land along highways and other rights-of-way full of weeds and grasses that can be converted to biofuel. It would cover the cost of mowing the public areas as well as generate revenue for the state.

The implementation will begin on a 10-plus acre parcel as well as the original test plot in order to create standard operating procedures and plans to scale it up in other areas across the state. They plan on using the biomass for heating Illinois Department of Transportation garages and a new biomass boiler, as well as looking into biofuels using hydrolysis, fermentation, and gasification technologies.

New frontiers in using food waste

Again, ethanol was in the news in August when researchers from Penn State found a more efficient and less expensive way to convert potato waste into ethanol, which is good news for the more than 20 potato chip manufacturing companies located in the region.

By adding a bioreactor of mold and yeast while breaking down potato peels and residuals from complex carbohydrates to simple sugars and fermentation, researchers found it encouraged biofilm formation and larger numbers of microbes which helped improve ethanol production.

Ali Demirci, professor of agricultural and biological engineering, told Penn State News “This research is of great interest to Keystone Potato Products in Hegins, Pennsylvania, a subsidiary of Sterman Masser Inc. The company is paying attention to this project, hoping this novel approach may help it add more value to its waste potato mash. Industrial food wastes are potentially a great substrate in production of value-added products to reduce the cost, while managing the waste economically and environmentally.

#9: New processes and organisms

High-pressure pre-treatment before fermentation sparks big boost in yield

Last month, we reported that new research from a professor of engineering at UBC’s Okanagan Campus might hold the key to biofuels that are cheaper, safer and much faster to produce. Starting with materials commonly found in agricultural or forestry waste—including wheat straw, corn husks and Douglas fir bark—she compared traditional fermentation processes with their new technique and found that Douglas fir bark in particular could produce methane 172 per cent faster than before.

The new process pretreats the initial organic material with carbon dioxide at high temperatures and pressures in water before the whole mixture is fermented, she explained. The new pretreatment process uses equipment and materials that are already widely available at an industrial scale, so retrofitting existing bioreactors or building new miniaturized ones could be done cheaply and easily.

Advanced yeasts

In June, we reported that Xylogenics released a new strain design for its patented GX-1 yeast production and fermentation process. Xylogenic’s latest strain is currently applicable within the fuel ethanol industry and will soon be available to markets as varied as pharmaceuticals, agriculture, enzymes and a variety of bio-based chemical products such as flavors, fragrances, plastics, and solvents.

The Xylogenics’ team of scientists has the experience to take a project from custom yeast design to scale-up and commercialization with expediency

Advances in e.coli

In July, we reported that researchers at Arizona State University wanted to squeeze out more energy from xylose sugars. To do so, they challenged E. coli bacteria that could thrive comfortably on glucose — and switch out the growth medium broth to grow solely on xylose. The bacteria would be forced to adapt to the new food supply or lose the growth competition. The bacteria, when challenged, randomly mutated their DNA until it could adapt to the new conditions. They held on to the fittest mutations over generations until they became fixed beneficial mutations.

And in each case, when challenged with xylose, the bacteria could grow well. Their next task was to find out what these beneficial mutations were and how did they work. To grow better on xylose, the three bacterial E. coli lines had “discovered” a different set of mutations to the same genes. The single mutations the research team identified all could enhance xylose fermentation by changing bacterial sugar metabolism.

#10 Effective Execution

In our Thought Leadership series, experts like Mark Warner and Jeff Lievense regularly share the latest on effective execution in taking advanced fermentation processes to scale.

The Digest’s 2017 Multi-Slide Guide to Advanced Fermentation 3.0 – The Must Knows

Scale-up from Pilot to Commercial: The Digest’s 2016 Multi-Slide Guide to Fermentation 2.0.1

Advanced Downstream Recovery: Converting fermentation broth into products

Scaling-up through contract manufacturing

Commercializing Innovative Foods