Contributed by Coralie Martin, Communication, Marketing and IR Manager, Deinove; Dennis McGrew, Chief Business Officer, Deinove
More consumers are seeking out products labeled as “natural.” This is especially true in some specific market segments, such as the cosmetics market and the food and feed sector, in which consumers are increasingly sensitive to the “naturality” of the ingredients.
How can we meet this growing demand when natural resources are limited? By developing new sustainable production methods! Biotechnological production is a path which must be explored further. It is widely applied to pharmaceutical manufacturing, but much less common for the production of daily consumer goods.
We at DEINOVE, a France-based industrial biotech company, work to address this challenge by developing new production modes for the industry that are responsible, sustainable and cost-efficient. Our innovative green solutions advance the use of renewable feedstocks and their viability is evidenced by our ability to scale up and accrue industrial partnerships.
DEINOVE’s technological platform
During the early stages of the company, DEINOVE’s research team was busy collecting bacteria samples around the world, especially on mainland France and French overseas territories. They collected samples from extreme environments like deserts, glaciers, hot springs, volcanoes, lagoons, and tropical forests in order to target particularly resistant strains of higher value for industrial applications.
The company has built a large bacterial library now containing more than 6,000 strains – some of which are fully sequenced and annotated - and has developed a technology platform that enables it to:
- select the best strain profile in terms of growth and metabolic capacity
- optimize these strains by genetic engineering (overexpression of the targeted metabolic pathways, elimination of competing pathways) – if so required - and fermentation engineering (optimization of culture and fermentation processes, optimization of substrates)
- validate these new production systems by scaling up processes
DEINOVE’s bacterial library
It took DEINOVE’s team four years to harvest the strains in these numerous hostile biotopes. Using a patented selection method consisting of irradiating the environmental samples, the company collected 6,000 strains, rare and extremophile, with unique metabolic capabilities. Many bacterial phyla are represented in this strain bank, and thus might be exploited: Actinobacteria, Proteobacteria, Bacteroidetes, Firmicutes… including one genus, which is totally uncommon: Deinococcus.
This variety of strains give access to a wide range of naturally-occurring compounds, which are of interest for industrial use, such as carotenoids, lipids, cell walls, exopolysaccharides, enzymes, osmolytes, etc. DEINOVE is committed to harnessing this strength.
A few words about Deinococcus bacterium
This non-pathogenic bacterium is known as one of the oldest life forms on earth originating about 3 billion years ago. It is well known for being extremely resistant to radiation, dessication and other stress factors. D. radiodurans for example is 50 times more resistant than Escherichia coli to ionizing radiation. It was first isolated in 1956 when canned meat was found spoiled even though it had been exposed to radiation, a sterilization method.
The organism can withstand massive doses of radiation and can even survive being completely dried out. When that occurs, "The genome is shattered into hundreds of pieces. It is a dead cell,” Miroslav Radman, author of the study, said. "But out of this horrendous damage, it can resurrect.” Given these outstanding resistance properties it's not difficult to imagine the potential of such bacteria for biotechnological applications!
This led to the creation of the company DEINOVE in 2006, the sole company exploiting these bacteria for industrial processes. Leveraging the thermophilic properties of Deinococcus bacterium, its ability to use polymeric sugars and the production of enzymes, the initial focus of the company was the production of second-generation bioethanol. The important work done within this project has enabled development of a unique metabolic engineering platform and successfully established the Deinococcus as a novel host for industrial production – whether for commodities, chemical intermediates or specialties.
Deinococcus: a natural carotenoids producer
Deinococcus bacteria naturally produce carotenoids. Interestingly, their carotenoid-containing lipid membrane explains its red pigmentation and, among other factors, allows for its remarkable resistance.
Carotenoids - beta-carotene, alpha-carotene, lutein, zeaxanthin, lycopene, astaxanthin, to name but a few - are compounds of industrial interest. These are widely used as colorants in food and feed (color of choice for pigmenting fishes for example) and as antioxidants in cosmetics and nutritional supplements. Nutritional supplements is the fastest growing segment.
Distinguished by their orange, yellow, and red pigments, carotenoids are found in some plants, algae, and bacteria. Carotenoids act as antioxidants within the body, protecting against cellular damage, the effects of aging, and even some chronic diseases. These beneficial compounds cannot be synthesized by humans or animals; diet is the only way to get them. About 75 % of existing production consists of petroleum derivatives; the rest is produced by plant extraction, or fermentation, mainly from fungi or microalgae. The natural carotenoid sector is growing, particularly benefiting from consumer demand. Yet, supply of bio-based solutions remains limited by high production costs related to low production yields and to the limited availability of raw materials (seasonality, sustainability, etc.). Consequently, biotechnological production is a good option to combine natural production processes and industrial performance.
DEINOVE’s competitive advantages
Deinoccocus shows critical benefits for the carotenoid production compared to the existing biotechnological processes:
- they multiply quickly: their growth rate is much higher than that of Haematococcus pluvialis (reference algae for the production of astaxanthin, for instance) ; 0.6 h-1 vs. 0.05
- they have a high cell density (50-60 g/l vs. 5-7 g/L astaxanthin producers), thus reducing production costs
- they can produce carotenoids naturally from diverse feedstocks (C6 sugars, C5 sugars, polymeric sugars like starch)
- the production equipment is cheaper than photobioreactors
- the quality of the final product is consistent
In addition to favorable natural capacities, DEINOVE benefits from its high-throughput metabolic engineering platform to improve the performance of the strains and achieve significant production levels, suitable for industrial applications, giving the company a real competitive advantage. It should be noted that, in such circumstances, the final product is GMO-free even if its production is not.
Progress and next steps
The DEINOVE teams have optimized strains for the production of carotenoids that have already been approved for commercial purposes. Proof of concept has been obtained in the laboratory for five molecules. Optimization of the strain by the high-throughput genetic engineering platform has increased product yields by a factor of 6 to 8 compared to initial performance and thus achieving, for some of these molecules, satisfactory levels for subsequent scale-up.
DEINOVE aims to commercialize several carotenoids within two to three years whose production will be ensured by production partners. The next steps of the program are:
- Improvement of final yields and production volumes;
- Development of extraction and purification of these carotenoids to obtain a marketable product;
- Validation of the functional benefit of the molecules produced;
- Continuing regulatory proceedings for market authorization.
DEINOVE could become a real game-changer in the way we produce innovative natural ingredients. Major industrial players have already wagered on the wealth of the DEINOVE strain bank, starting with Avril and Flint Hills Resources (Koch Industries) who rely on DEINOVE for the production of ingredients for animal nutrition. DEINOVE focuses on screening its bacterial library, to identify and optimize the bacterium that are able to produce the targeted compounds in acceptable quantities at competitive economics.
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