The Best Industrial Microorganism You've Never Heard Of

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June 6, 2014

Since there wasn't enough news this week for a SynBioBeta Weekly Wrap I thought we could dive into a unique technology platform that reached two important milestones in early June. Deinove may be unknown to many in the synthetic biology community (it's based in France), but the industrial biotech is pioneering a platform capable of producing ethanol, enzymes, antibiotics, chemical intermediates, and other green chemicals from processed biomass feedstocks without additives (enzymes, yeast, antibiotics). What is the secret to the platform's envious potential? Deinove has harnessed the unique capabilities of Deinococcus bacteria, most of which evolved to survive the harsh conditions of Earth 3.5 billion years ago. That's sure to translate to robust industrial performance.

Deinococcus advantages

Early Earth wasn't the lush paradise it resembles today. In order to survive Deinococcus strains had to develop novel cellular processes that resisted radiation, oxidation, heat, drought, and cold -- all of which can damage DNA. Other organisms have developed similar capabilities to protect themselves, but when bacterial chromosomes become fragmented the damage is often irreversible. That's not true for Deinococci, which are able to reassemble hundreds of chromosome fragments with near perfect fidelity by storing up to nine copies of their chromosome and implementing a simple repair mechanism to restore DNA in a matter of hours after damage occurs. (That alone sounds like a cellular process that could be leveraged to develop a novel gene editing/assembly technology. We jacked CRISPR from bacteria, why not something like this?)

Image Source: Deinove.

Image Source: Deinove.

In other words, Deinococci are extremely robust organisms, which is exactly what you want in an industrial microorganism. Deinococcus can naturally endure physical (no shearing from agitation) and chemical stress experienced from an industrial environment. In fact, strains ferment ethanol from second-generation feedstocks at 50 Celsius (122 Fahrenheit).

In addition to withstanding punishing blows to their genomes, Deinococci are able to stably integrate genes from other organisms (bacteria, yeasts, plants) into their genome on an unprecedented scale. That greatly aids Deinove during strain development and metabolic pathway engineering, as does the company's world-leading library containing 6,000 strains.

Industrial applications and strategy

Deinove is pursuing three unique product application areas with its platform: second-generation ethanol (DEINOL), green chemicals (DEINOCHEM), and antibiotics (DEINOBIOTICS). The company's ethanol program has progressed tremendously in recent years. After announcing an initial yield of 3% w/v several years ago, Deinove announced a 9% w/v yield in January 2014. That demonstrates the potential economic viability of the production process and landed a collaboration agreement with Abengoa -- a world-leading renewable technology company. Deinove is also working with Suez Environment, a world-leading waste processing and recycling company, on a waste-to-fuel research and development program for converting urban organic waste to second-generation ethanol with its platform.

Image Source: Deinove.

Image Source: Deinove.

In green chemicals, Deinove has identified the isoprenoid pathway as its first commercial pathway target. Sound familiar? That's because it's the same metabolic pathway being pursued by synthetic biology pioneer Amyris. While there could very well be competition and overlap between the two companies, over 22,000 compounds have been identified in the isoprenoid pathway, including flavors, fragrances, cosmetic creams, detergents, pharmaceuticals, and more.

Deinove has chosen three broad categories to focus on initially: (1) highly aromatic compounds (linalool, geraniol, myrcene, limonene or lycopene) for use in perfumes, cosmetics, and household products; (2) carotenoids for food and animal feed applications; and (3) isoprene for performance materials. To my knowledge, the only overlap with Amyris' commercialization targets is isoprene (being developed with Michelin), although there is bound to be overlap in aromatic compounds, too.

And finally, in antibiotics, Deinove is focusing its efforts on 12 unique Deinococcus strains: including nine with activity against Gram-positive pathogens and two with broad activity. The company has created a wholly-owned subsidiary to separate this program from its other commercial goals.

The Deinococcus way

I think readers should takeaway several key points from Deinove's novel industrial biotech platform. First, there are many, many more host organisms with industrial potential beyond the standard hosts (yeast and E. coli). There are many companies emerging with expertise in yeast engineering -- and rightfully so after Amyris went all-in in the area -- but don't limit your research, investment, or entrepreneurial dreams to the standard hosts. Remember, Deinove enjoys an unrivaled intellectual property position from developing an expertise specific to its host.

Second, the company's platform illustrates the extreme diversity and robustness of biology. Chances are, if you need a gene or enzyme for a specific function, an organism exists somewhere with at least a starting copy of it.

And third, just when you think you know every synthetic biology company in existence because you live in San Francisco, Boston, or London; one emerges that somehow went undetected. This should become more common as tools improve in the coming years. Where will tomorrow's next great synthetic biology startups call home?

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