Lygos seems to have found a very advantageous niche for the biotech chemical industry.

All of humanity’s earliest civilizations were built around fermentation products such as wine, vinegar, and cheese. During the 19th century, Louis Pasteur and others begun to unravel how fermentation was caused by simple microbes, which started the shift from “ancient biotechnology” to what we know today as industrial biotechnology.The acceptance of the fermentation industry was bolstered by Chaim Weizmann’s production of acetone from Clostridium acetobutylicum, a crucial technology that helped supply Britain with enough acetone to fight and ultimately win World War I. However, this success story was not enough for industrial biotechnology to compete with the rise of the petrochemical industry, and chemical production via fermentation began to decline.

Shifts in advantage

The major costs associated with the petroleum industry have always been determined by the extraction of oil and natural gas. Some of these costs were mitigated as product streams were diversified during the mid 1900’s. For instance, a single petrochemical like benzene can now be used to manufacture a multitude of derivatives, such as polystyrenes, polyurethanes, nylons, and epoxy resins making the whole process more economical. As such, we now use thousands of petrochemical products in our daily lives. Meanwhile, biotechnology was sidelined due to its relatively high costs and had to wait till the dawn of the 21st century for commercial realization.The costs affiliated with ventures in biotechnology were so great that even early genetic engineering couldn’t offer much to the fermentation industry. This is in large part because technical failure is only evident after huge amounts of money have already been invested in the construction and actuation of larger scale fermentation plants.In addition to this complication, industrial biotech has almost always targeted low value products, such as biofuels which ended up being an unfortunate and short-sighted endeavour.The idea was that the high market penetration of fuel would ensure that, if produced inexpensively, the biofuels would be purchased. However a very major technical hurdle lay in the way. Unlike raw materials in the petrochemical industry, which are almost entirely composed of carbon and hydrogen, the biotech industry relied on sugar as their raw material and microbial feed source. The problem being that sugar, by mass, is composed of 51% oxygen, an element that is essentially thrown away during the production of hydrocarbon fuels. This explains why biofuels are so economically inefficient; biotech companies throw away over half of the raw material they have to purchase.However, there are chemicals that can be produced through biological production more efficiently than by petrochemical derivation. Such chemicals, where biology holds an upper hand, are termed bioadvantaged chemicals, and this is where the resurgence of industrial biotechnology is taking place.One such development is the recently constructed, inaugural pilot scale facility capable of malonic acid production from a renewable source by Lygos (@LygosBiotech), a synthetic biology company. Lygos was founded by Eric Steen, Jeffrey Dietrich, Jay Keasling, Leonard Katz, and Clem Fortman in 2007 and is the first spin out of the Joint Bioenergy Institute. The company is heavily investing in new-age metabolic engineering and feedstock diversity to compete with petroleum as a method of producing chemicals renewably.

Organic acids lead the way

The absence of oxygen in biofuels may have defeated that particular prospect, however organic acids can be produced in an economically efficient manner since they are rich in oxygen, and would utilize all the mass of the sugar feed source. A look at the theoretical mass-to-mass conversion from sugar makes it clear how organic acids are a safer bet than alcohols. The yields for biodiesel, biobutanol, and bioethanol are in the range of 35-51%. While for lactic acid, citric acid, and malonic acid, the yields would be as high as 100-113% (astonishingly high numbers made possible by the microbes ability to fix carbon from environmental CO2).Lygos collaborated with the Advanced Biofuels Process Determination Unit of Lawrence Berkeley National Lab to scale-up the production of malonic acid. It is an intermediate to many fragrances, pharmaceuticals, polyesters, and other chemicals with a collective worth of over $1 billion. Unlike many companies before them, the process metrics observed in the lab were found to be replicated during their pilot scale processes.Although production of organic acid unsurprisingly lowers the pH in the fermentation medium, Lygos developed a suite of metabolic engineering tools to engineer yeast and fungi that can tolerate the acidic levels. They even spun this to their advantage, explaining that the acidic environments reduce the possibility of contamination.The biological production of malonic acid provides other benefits in addition to its cost effectiveness. Production of organic acids from petrochemicals requires requires toxic inputs like sodium cyanide, while Lygos’ method eliminates the need to do so, all the while, it decreasing carbon dioxide emission and running more energy-efficiently.

Lygos seems to have found a very advantageous niche for the biotech chemical industry.

Beating petroleum at its own game

However, the biotech industry doesn’t need to forgo biofuels forever. The petrochemical industry’s ability to produce multiple products from oil and natural gas is its main advantage. If biotech is to compete, the oxygen stripped from the sugar molecule while producing alcohol must be put to some use for biofuel to be economically viable. Biorefineries hold the key to do so.A biorefinery is a facility that integrates thermochemical processes with biochemical processes, and biofuels production with biomass transformations. As of now, biofuel production involves production of either ethanol, biobutanol, or biodiesel in a standalone unit from a single feedstock. Analogous to a petrochemical refinery, a biorefinery will make it possible to produce a wide range of fuels and valuable by-products from multiple feedstocks.Advances such as these would liberate industrial biotechnology from its failures of the last century and pave the way for a greener future. Science is not the challenge, technology (read scale-up) is.Find this article interesting? Join us at SynBioBeta London 2015 where the synthetic biology community will gather to hear from the companies, like Lygos, commercializing their cutting edge research.