Companies Developing Modified Microorganisms for Ethanol Production (part 1)

In this entry of the blog, I’ll discuss the companies that are using biotechnology to improve microorganisms that are used to produce ethanol (typically cellulosic ethanol). This is one of the industry sectors that has the longest history and also where the greatest amount of biological research has been carried out over the years. The production of ethanol for fuel use is of course an extension of long-practiced methods of fermentation used for food and drink since antiquity. Mankind first discovered the phenomenon of fermentation thousands of years ago, in noticing that liquids derived from various kinds of plant matter such as the juice of fruits would over time become transformed into substances having very different properties and tastes. This phenomenon was ultimately domesticated for the production of wine, beer, other fermented beverages, as well as foods like cheese, yogurt, and preserved foods, although the microbial basis for this process was of course not understood until fairly recently (i.e. the mid nineteenth century).  

Because of this long history, and the accumulated biological and engineering knowledge relating to ethanol fermentation, it was only natural that various industrial uses for ethanol would be investigated, including its use as a fuel or gasoline additive. Ethanol was first used as a transportation fuel in Brazil in 1975 and in the U.S. in 1978 (in the form of a 10% blend then known as “gasohol”), and received a great deal of attention in those years due to the oil embargo and gasoline crisis of 1979. Although interest in ethanol as a fuel died down once the price of gasoline began to decline, this initial spike of interest coincided in the U.S. with the development of recombinant DNA research tools and the subsequent growth of the commercial biotechnology industry, and so speculation about the ability of genetic engineering to improve ethanol production dates back to the very early years of the biotech era. One of the first government reports on the industrial and commercial potential of new genetic technologies, the April 1981 report by the (now-defunct) Congressional Office of Technology Assessment entitled “Impacts of Applied Genetics: Micro-Organisms, Plants and Animals” included as one of its appendices a lengthy case study on how genetics might improve production of ethanol (see page 293 of this report, at Google Books). I worked at one of the earliest biotech companies to spring up in Cambridge, Mass. beginning in 1981, and improving yeast strains for enhanced ethanol production, particularly by imparting the ability to degrade cellulosic feedstocks, was one of several early projects we contemplated.  

I go into this long introduction to make the point that scientists have been trying to enhance microbial production of ethanol for a long time, even predating the biotech revolution in the 1970s. To be sure, advances of various kinds have been made over the last three decades, but the fact that the problem is not yet “solved” and that many researchers are still tackling the problem indicates the inherent limitations and difficulties that are being faced. One limitation is the fact that while some fermentation organisms have evolved, acquired or been selected for the ability to survive and thrive at high ethanol concentrations, most other microorganisms cannot tolerate such high alcohol levels, so improving fermentation efficiency enough to significantly increase ethanol concentrations in the fermenter may wind up killing the production organisms. With some exceptions, this means that most bioethanol genetic engineering takes place in host microbial strains that are already capable of fermenting sugars to ethanol and in tolerating relatively high ethanol concentrations. The challenge has been to have these species express other enzymes and pathways that, for example, enable the degradation of the complex celluloses, hemicelluloses, and lignins found in cellulosic feedstocks.   

Although the historical progress of research in this field has been slow, it is likely that cellulosic ethanol will be the first sector of the biofuels industry to see the widespread use of genetically modified or engineered microorganisms. This is true for several reasons. First, many of the companies in this sector of the industry have had a “head start” – companies like Verenium and BioEnergy have been pursuing microbial approaches to cellulosic ethanol production since the 1990s, and all the companies in the sector benefit from the long years of prior research. Second, many of these companies are working with host organisms (e.g. E. coli, various yeast species) that are well studied, with well-known characteristics and safety profiles, and with well-worked-out methods for large-scale fermentation.  Third, there is an existing, growing, industrial infrastructure for the production, transportation and sale of ethanol produced by fermentation of biomass, and the existing manufacturing facilities and other commercial infrastructure can be used for processes involving modified microorganisms with little or no modification. Finally, the ability of U.S. producers to meet the very ambitious levels of ethanol manufacture mandated by federal law (the Renewable Fuel Standards), and to do so without overly relying on food crops such as corn, would seem to depend on the availability of technological breakthroughs to enhance the efficiency and output of ethanol production or to broaden the range of non-food feedstocks. These are problems which can be addressed using genetic engineering.  

There are some reasons to be more cautious in forecasting widespread use of modified microorganisms in ethanol production, although most of these reasons have to do with the current standing of ethanol within the renewable fuels world. In short, ethanol has gotten a bad rap lately. Because of continuing concerns that significant increases in biomass production of ethanol will lead to either deforestation or crop shortages accompanied by commodity price increases, and because of reports that ethanol production may require more energy than it produces or that it has an unfavorable carbon footprint, many observers are skeptical that ethanol will have a long-term role to play in the universe of renewable fuels. Many have written off corn ethanol for exactly these reasons, and while cellulosic ethanol produced from non-food crops overcomes some of these concerns, other concerns are of a more general nature and to they extent applicable, they may limit the usefulness of ethanol as a fuel. On the other hand, the types of genetic improvements being contemplated by this sector of the industry, perhaps coupled with use of the genetically engineered plant feedstocks I’ll discuss in a later installment of the blog, could provide the technological push to overcome unfavorable economics, energy balance or carbon footprint.  

The following table lists the companies that that are developing engineered or modified microorganisms for the production of ethanol. Brief profiles of these companies will be posted in “Part 2” of this blog post.  

  • BioEnergy International
  • DuPont Danisco Cellulosic Ethanol LLC
  • Glycos Biotechnologies
  • GreenTech America
  • Joule Biotechnologies*
  • Mascoma Corporation
  • Microbiogen Australia Pty Ltd. (non-GMO)
  • Promethegen Corporation
  • Qteros
  •  TMO Renewables Ltd.
  • Verenium Corporation

Several of these companies are also developing other fuels, and those marked with asterisks will be profiled in later sections of the blog. 

D. Glass Associates, Inc. is a consulting company specializing in several fields of biotechnology. David Glass, Ph.D. is a veteran of nearly thirty years in the biotech industry, with expertise in patents, technology licensing, industrial biotechnology regulatory affairs, and market and technology assessments. This blog provides back-up and expanded content to complement a presentation Dr. Glass made at the EUEC 2010 conference on February 2, 2010 entitled “Prospects for the Use of Genetic Engineering in Biofuel Production.” The slides from that presentation are available at http://www.slideshare.net/djglass99.

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