Overview of Companies Applying Advanced Biotechnology to Biofuels

The strategies described in the earlier entries in this blog are being pursued by a number of companies in the U.S. and elsewhere to bring about improvements in the commercial production of ethanol, biodiesel and other biofuels. In the next several entries, I’ll discuss the companies that are pursuing biotech strategies to produce the different classes of biofuels. In each entry  I’ll focus on one industry sector, and I’ll analyze the issues facing the use of biotechnology in that sector, I’ll assess the prospects for commercial success, and I’ll provide brief profiles of the companies actively developing modified organisms or conducting biotechnology R&D within that sector. 

The companies I’ll be focusing on are all in the category one can call “technology providers”, specifically biological technology providers, and these companies generally fill a well-defined niche in the industry, and their technologies play well-defined roles in the fuel production lifecycle. The existing infrastructure for production of ethanol and other biofuels includes companies across the whole spectrum of activities including growing and harvesting the feedstocks, pretreating the biomass, operating the fermentation or other conversion process, separating and purifying the resulting fuel, and finally storing, selling and transporting the fuel. The companies I’ll be profiling are all creating or developing improvements in any of three particular phases of the production process: 

  • improving the cellulosic or leafy plants or other vegetative material that are the feedstocks for fuel production.
  • improving methods of treatment or pretreatment of the biomass.
  • improving the microorganisms, algae or enzymes that perform or catalyze the fuel manufacturing process.

It is true that the biofuels industry includes technology developers other than those I’ll be profiling, particularly including companies developing improvements in chemical or physical processes that are used at various points in biofuel manufacture, but my focus here is on improved biological technologies. I would also note that many of these “biotechnology providers” are also developing technological improvements in other aspects of the production process, such as the downstream processing steps, further blurring the lines between different categories of companies. Such activities are also an example of the kinds of interesting routes to diversification that many companies are taking to maximize their chances for success in the market, a strategy I’ll discuss in later installments of the blog. 

I’ll also try to observe a further distinction among the biological technology providers. Ethanol, biodiesel and other fuels can be, and have historically been, produced without the use of advanced technology, utilizing many types of organic biomass not having any special properties (notably including waste materials of many kinds) and utilizing naturally-occurring, non-selected varieties of microorganisms or algae. For the most part I will not discuss those companies in the biofuels business that are using or selling nonproprietary components, naturally occurring microorganisms, or traditionally-bred plant varieties, and instead I will be directing my attention to those companies that are using or developing proprietary compositions, methods and techniques using genetic engineering or other advanced biotechnology. However, this is not a bright line distinction, and some of the companies profiled, particularly in the algae sector, are using naturally occurring organisms that have been selected or enhanced using traditional techniques rather than by genetic engineering. With regard to the microorganism and algae companies, I will generally include a company if the organism central to its commercial process is genetically modified, selected or enhanced in any way, or is otherwise “proprietary” to the company. With regard to new plant feedstocks, I will not include companies that are developing or selling plant varieties developed using conventional crop breeding methods, but only those that are developing genetically engineered plants, or that are using biotech methodologies to aid or enhance traditional breeding. 

The entries that follow will summarize the following sectors of the industry:

  • Modified microorganisms for ethanol production.
  • Modified microorganisms for butanol or isobutanol production.
  • Modified microorganisms (including “synthetic” microbes) for production of biodiesel, jet fuels, and other petroleum-based fuels.
  • Use of modified microorganisms or plants to manufacture industrial enzymes.
  • Modified algae for biofuel production (biodiesel, jet fuel, ethanol and other fuels).
  • Modification of traditional plant feedstocks (e.g. for ethanol production).
  • Modification of new or alternative plant feedstocks for production of ethanol or biodiesel.

The company profiles in the entries that will follow are based on publicly-available information, and include descriptions that have been adapted or excerpted from company websites. URLs will be provided for all profiled companies.

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 www.slideshare.net/djglass99.

Presentation at EUEC 2010 Conference, 2/2/10

I’ll be traveling to Phoenix next week to present a talk on the prospects for the use of advanced biotechnology in commercial biofuels production. This talk, on Tuesday, February 2, will be at the EUEC 2010 Energy and Environment Conference, and I’m a co-chair of a session in the “Biofuels, Biomass & Biogas” Track, entitled “Biofuel Ethanol”. My original motivation to start this blog was to be able to present additional information to supplement this presentation that I won’t have the time to present in the talk. My blog posts to date have covered some of the introductory sections of the talk (mostly providing an overview of the types of biotech strategies that are applicable to different industry sectors and to different classes of organisms). I will continue to post additional content that supports my talk, beginning later this week with discussions and profiles of those companies actively commercializing or researching applications of biotechnology in biofuel production. The first blog post covering the content of the talk is at http://wp.me/pKTxe-7

I’ll be attending two days out of the 3-day EUEC meeting, and during my time at the conference, I’ll be blogging about any interesting presentations I attend or other information I learn about biofuel-related activities. After the talk, I’ll be posting my slides online, and there will be a link to the slides here in the blog – look for that by the end of the first week in February. As always, please feel free to comment or contact me with any questions you may have.

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 is making at the EUEC 2010 conference on February 2, 2010 entitled “Prospects for the Use of Genetic Engineering in Biofuel Production.”

Strategies to Engineer Plants for Use as Biofuel Feedstocks

There has recently been increasing interest in using genetic engineering or other advanced biological technologies to improve the plants that are used as feedstocks for production of ethanol or other fuels. Some efforts are being directed at food crops like corn: even though most observers today consider corn ethanol to be a transitional fuel, the techniques for genetic engineering of corn are well known and easily practiced, and there are a number of companies that consider corn to be somewhat of a “model crop” and only a short-term product opportunity. Efforts are also ongoing to engineer the plant species that might be alternative biofuel feedstocks , including trees, switchgrass, oil-rich crops like canola or Jatropha and others. The following is an overview of some of the approaches being taken to engineer plants for biofuel use: see Sticklen 2006; Torney et al. 2007; Sticklen 2008; and Weng et al. 2008 for more comprehensive scientific reviews of research in this field. 

Techniques for genetic engineering of plants have been well-established for over two decades, with the earliest methods for transforming dicotyledonous plants being developed in the mid-to-late 1980s and methods for transforming monocots (including most of the world’s important cereal crops) arriving several years later. In many ways, the methodology resembles the techniques used to engineer microorganisms, but with the added challenge of successfully transporting the exogenous DNA through the plants’ cell wall (a feature unique to plants) en route to the cell nucleus. Among the methodologies to accomplish this are the use of Agrobacterium, a microorganism naturally having the ability to inject its DNA into plant cells; electroporation, in which the DNA is transported into plant cells using electric current; and the “gene gun”, where DNA is adhered to extremely small nanospheres which are shot at high velocity into the cells. 

Some of the possible technological approaches to using plant genetic engineering to improve biofuel production are summarized in below. The most common strategies for creating transgenic plants for use as biofuel feedstocks have as their goal the introduction of genetic changes into certain plant species to make them more useful for the production of ethanol and other fuels. For example, one might introduce genes encoding key biodegradative enzymes such as cellulases or ligninases into the plants, to enhance the conversion of cellulose into fermentable sugars, thereby improving the pretreatment of cellulosic feedstocks. Other companies and research groups are focusing on engineering oilseed crops to have altered or enhanced lipid content, to make them more suitable for production of biodiesel (analogous to strategies used for altering algal strains). 

Genetic Engineering Strategies: Plants

  • Overexpress cell-wall hydrolysis enzymes.
    • Cellulases
    • Hemicellulases
    • Ligninases
  • Increase plant biomass, cellulosic biomass.
    • Cellulose biosynthetic enzymes.
  • Lignin modification to reduce need for pretreatment.
    • Down-regulate lignin biosynthesis.
  • Regulated gene expression, so traits are active only when needed.

Another approach is simply to engineer or breed biofuel crop species to grow faster and/or create more biomass.  It has also been proposed that one might engineer plants, particularly trees, to have reduced lignin content, which might greatly facilitate the pretreatment steps now needed to process cellulosic feedstock into fermentable sugars. One intriguing step towards this goal was recently achieved by a group from Brookhaven National Laboratory, who used protein engineering to alter a plant enzyme that catalyzes the synthesis of certain lignin precursors, so that the enzyme instead produced molecules unable to serve as the building blocks for lignin (this engineered enzyme has not yet been tested in plants).  

A number of companies and research groups are taking these genetic engineering approaches one step farther, with the goal of using gene expression promoters capable of being regulated so that key degradative enzymes would not be expressed in the plant tissue until the specific time they are needed.  In this way, transgene expression would remain silent during the normal growth of the plant, but expression would be turned on during pretreatment or processing or at a similar stage when expression of the degradative enzyme is most needed. Companies pursuing this strategy include Agrivida and Farmacule Bioindustries

Finally, there are also several companies that are developing genetically engineered plants as “factories” for the production of enzymes for use in fuel fermentation. Similarly to companies using microorganisms to produce cellulytic or other degradative enzymes, some of these companies (like Medicago) are ones that are already in the business of creating transgenic plants for the commercial production of enzymes or other industrial products, or pharmaceutical products. One such approach is being taken by the seed company Syngenta, which has received approval in several countries (but not the U.S.) to commercially sell a strain of corn that has been engineered to overexpress an amylase enzyme, for use in biofuel production. 

Later entries in this blog will discuss the programs and strategies of commercial biotech companies that are developing modified plant varieties for biofuel use. At this writing, I’m aware of at least 15 companies in the U.S. and elsewhere in the world that are actively pursuing such goals.

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 www.slideshare.net/djglass99.

Strategies to Engineer Algae for Biofuel Production

Researchers have investigated the possible use of algae for biofuel production for many years, dating back at least to efforts by the U.S. Department of Energy in the 1970s. These early efforts failed to result in production technologies that were economically competitive with petroleum-derived fuels, and so the field stagnated. However, recent years have seen an increased interest in the use of algae to produce biodiesel and other fuels. Within the past couple of years, most of this renaissance was fueled by news of several big business deals involving algal biofuel firms, particularly the research partnership between ExxonMobil and Synthetic Genomics for development of improved algal strains using synthetic biology. With this renewed interest has come increased activity in the application of biotechnology to improve the strains of algae that might be used in biofuel production, thus providing process improvements that could make such methods economically competitive. I’ll briefly summarize some of the biotechnology strategies that are being used or that have been proposed, again with the caveat that this is cannot be a comprehensive scientific review. Among published reviews are Rosenberg et al. 2008, Li et al. 2008; Angermayr et al. 2009 and Mayfield (undated).

Of the three classes of organism that are amenable to improvement for biofuel purposes, algae are the laggards with regard to the development of technologies to enable reliable, stable genetic transformation. A number of algal strains can be genetically engineered, and in fact, engineered algae have long been proposed for use in industrial production of pharmaceuticals and other high value products. But according to Rosenberg et al, “routine transformation has only been achieved in a few algal species” in spite of significant and ongoing progress in extending such techniques to other species. Techniques exist, or are under development, for targeting genetic changes either to nuclear DNA or chloroplast DNA of microalgae species. 

The biofuel strategy most often contemplated for algae is the large-scale production of biodiesel, jet fuel, and other petroleum-derived fuels. Biodiesel is usually composed of a mixture of fatty acid methyl esters, which can be produced from any biologically-derived source of fatty acids, with the final product created by a transesterification reaction. Mixtures of these esters can mimic the composition of petroleum-derived fuels such as diesel, jet fuel and others, which are complex mixtures of linear and branched hydrocarbons and cyclic alkanes. So, most genetic engineering strategies contemplated for algae involve enhancing or altering natural lipid biosynthetic pathways, to create a mixture of fatty acids suitable for conversion to biodiesel or other hydrocarbon-based fuels. One example (described in Rosenberg et al) is to transform an algal strain to express one or more enzymes involved in lipid biosynthesis – the example given in Rosenberg et al. is the enzyme acetyl-CoA carboxylase, which in early experiments was engineered into an algal strain, albeit with little impact on lipid biosynthesis. It has been reported that Aurora Biofuels is pursuing a similar approach to the enhancement of lipid synthesis in algae. 

Other approaches to engineering algae are described in the table below. Such ideas include finding ways to enhance the efficiency of photosynthesis in algal production strains  (e.g. by engineering the strains to synthesize large amounts of photoreceptor molecules), or to enable algae to utilize alternative food sources, particularly the ability to metabolize and ferment sugars. Solazyme has conducted research in these fields, and has pending patent applications relating to engineering light utilization and to alternate feedstocks for industrial algae strains. One unique approach that has been taken by Algenol Biofuels is to engineer cyanobacteria to express the enzymes pyruvate decarboxylase and alcohol dehydrogenase, allowing the algae to convert the common Krebs cycle molecule pyruvate first to acetaldehyde and then to ethanol, a strategy which the company is beginning to commercialize. Finally, it is also possible that genetic strategies might be used to attack what is a significant problem facing the use of algae to produce biodiesel: the need to separate the lipid products of the organisms from the aqueous medium in which the algae are grown. This often requires costly, energy-intensive physical processes, so that finding a biological method for secretion and sequestration of lipids from microalgae could be a very important development for the biofuels industry. Synthetic Genomics is reportedly trying to accomplish this goal using its synthetic biology expertise. 

Genetic Engineering Strategies for Algae.

  • Enhance algal growth rate.
  • Enhance or alter lipid biosynthesis.
  • Enhance photosynthesis.
  • Enable use of alternate food sources.
  • Enable secretion of lipids to aid oil/water separation.

The renewed interest in algal biofuels over the past several years has led to a lot of activity in the field, with many companies operating, building, or announcing plans to build pilot or demonstration plants, many of which might use algae modified using some of these approaches. I’ll discuss the companies in this sector of the industry, their technologies and commercial plans in later installments of this 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 www.slideshare.net/djglass99.

Strategies to Engineer Microorganisms for Biofuel Production

Much of today’s commercial activity using advanced biotechnology for biofuel production focuses on the creation, selection or improvement of strains of desired microorganisms having enhanced properties for functions important for biofuel production. Longstanding methods for producing ethanol or other fuels, generally rely on the use of one or more selected microbial strains to drive the fermentation process. Traditionally, these methods have made use of naturally-occurring or classically selected microorganisms, but in recent years the power of the new biotechnologies to develop enhanced strains is being investigated or used by numerous companies. The following is a brief overview of some of the strategies that are being pursued. This is not meant to be a comprehensive summary of such strategies, and it is well beyond the scope of this blog to try to provide a thorough review of the multitude of published scientific papers describing genetic engineering approaches to improving biofuels organisms. For those seeking more scientific detail, there have been numerous review articles published in recent years, including Dien et al. 2003; Jarboe et al. 2007; Stephanopoulos 2007; Atsumi and Liao 2008; Fortman et al. 2008; Lee et al. 2008; Rude and Schirmer 2009 and Connor and Liao 2009

 Typical strategies include: 

  • Overexpress desired enzymes within host fermentation organisms (e.g. to improve ability to process or degrade cellulosic feedstocks).
    • Alter the timing or amount of expression of native enzymes
    • Express heterologous enzymes from other species
    • Express synthetic or engineered enzymes
  • Engineer microorganisms to manufacture novel or improved industrial enzymes for stand-alone use in biofuel production.
  • Create novel or synthetic microorganisms to enable production of renewable fuels.

Perhaps the most common strategy employed to date has been the use of recombinant DNA techniques to engineer microorganisms to overexpress desired enzymes, including heterologous enzymes derived from other species which are not naturally found in the host species. This is the strategy most often used by companies developing new microbial strains for cellulosic ethanol production: it would be advantageous from a process perspective to have a single microbial strain that can express the cellulases needed to break down the complex components of cellulosic feedstocks while also possessing the pathways to ferment the resulting sugars into ethanol, but there are few, if any, naturally occurring microorganisms that combine these features.  One approach is therefore to introduce into host organisms that are already optimized for ethanol fermentation genes from other species encoding the desired cellulytic enzymatic activities. As another example, genetic engineering could be used to give ethanol fermenting microbes the metabolic pathways needed to utilize sugar sources such as the 5-carbon xyloses and other pentoses that are released from hydrolysis of woody biomass. The alternative approach would be to splice genes encoding the enzymes making up the ethanol fermentation pathway into an organism lacking that trait but having the ability to digest the complex cellulosic components. Strategies like these are being pursued by companies like Mascoma Corporation, Verenium Corporation and others. It is also possible to use genetic engineering simply to enhance the efficiency of naturally-occurring ethanol-producing strains that in some cases already have sufficient activity to be used commercially: an example of a company pursuing this strategy is Qteros, which is moving towards commercial use of a natural microbial isolate while beginning in-house research to improve its activity using biotechnology.   

A variation of this strategy is to create and use engineered microbes to manufacture novel or improved industrial enzymes, which can then be used as a catalyst in fuel fermentations to enhance or accelerate biofuel production processes. Enzymes like cellulases, amylases, and other degradative enzymes can be used to pretreat cellulosic feedstocks, or can be added to an ethanol production process at any other suitable time. Companies pursuing this strategy are generally companies already manufacturing and selling other industrial enzymes, including several companies having decades of experience in this sector of the industry, such as Novozymes, the Genencor division of Danisco, and others. The field has also attracted some newer players, such as Iogen Corporation and Dyadic International, some of which are devoting a significant portion of their effort to the manufacture and sale of biofuel enzymes.  

Finally, a more ambitious strategy is to use synthetic biology, metabolic engineering, or other advanced techniques to create novel or synthetic microorganisms possessing enzymatic capabilities not found in the original host organism. This strategy might involve designing an “optimal” organism using combinations of enzymes from other sources, or even completely new enzymes designed and created using protein engineering to have maximal catalytic activity. Strategies like these are most often being pursued to create microorganisms or algae optimized to produce “designer” mixtures of hydrocarbons mimicking the composition of diesel, jet fuels or other petroleum fuels, including efforts by companies like LS9, Amyris Biotechnologies, Joule Biotechnologies, and (in algae) by Synthetic Genomics.  However, this approach is also being used to enable more efficient production of other fuels: for example, Joule Biotechnologies is using synthetic biology to create novel organisms that use photosynthesis to produce ethanol and other transportation fuels from sunlight and carbon dioxide without the need for a biomass feedstock. 

I’ll have more to say about these and other companies in later installments of this blog, when I focus on specific sectors of the industry and the technology strategies being pursued in each. 

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 www.slideshare.net/djglass99.

Applications of Biotechnology to Renewable Fuel Production (Overview)

In recent years, as the need to develop alternative, non-petroleum-based transportation fuels has become more pressing, there has been a growing interest in using advanced biotechnologies to improve biofuel production. Specifically, numerous strategies have evolved by which biotechnology is being used to create improved biofuels products or processes, involving the creation of engineered or synthetic microorganisms for use in production of ethanol, biodiesel or other fuels, or genetically engineered (“transgenic”) plants as improved fuel feedstocks. These approaches can generally be summarized as follows.

Potential Applications of Biotechnology to Improve Renewable Fuel Production.

  • Enhanced or engineered microorganisms for fermentation of ethanol, butanol, other fuels.
  • Engineered microorganisms or plants to manufacture enzymes used in fuel production.
  • Improved algal strains for biofuel production.
  • Selected or engineered plant species with favorable traits for use as improved biofuel feedstocks.

There are a number of ways in which microorganisms, algae or plants can be modified for improved industrial performance.  Some of the companies and technologies I’ll discuss make use of selected, often proprietary strains of production organisms, that have been derived from naturally occurring organisms using traditional techniques of mutation and selection, or in the case of plants by traditional crop breeding. These methods have been practiced in industry and in agriculture for decades, and in many cases their use can lead to significant process improvements, for example in the efficiency of ethanol fermentation.

However, in most cases, the technology strategies I’ll discuss in this blog will be ones that utilize genetic engineering methods based on recombinant DNA. Recombinant DNA methods enable the insertion of genes from any source in nature into a chosen “host” organism, thereby conferring on the host organism a genetic trait or a biochemical capability not naturally found in that organism. Genes function in nature by encoding the synthesis of specific protein molecules, most of which are enzymes whose role it is to catalyze specific biochemical reactions inside living cells; and so by transplanting a gene into a new host organism, under conditions in which the gene can actively direct the synthesis of its corresponding enzyme, one can impart on the host organism new or improved biochemical powers. In the years since recombinant DNA techniques were first developed in the mid-1970s, techniques have been worked out for the genetic engineering of almost any species of organism having medical, industrial or agricultural value, including most important plant species, almost any microorganism, and many algal species. These techniques are now being used to improve natural processes for synthesis of ethanol and other fuels.

There are also a number of companies and academic research laboratories using more advanced technologies for improvement of microbial or plant performance. Many of these methodologies utilize recombinant DNA, but in ways specifically designed to facilitate the creation of organisms improved for a specific desired function. These newer techniques, along with more traditional methods of organism improvement, are summarized as follows, with the understanding that there can be some overlap in the way these terms are defined. Some of the technologies, like directed evolution or DNA shuffling, use a combination of genetic tricks and enhanced selective pressure to greatly enhance the activity of a targeted enzyme or pathway, while other techniques like synthetic biology allow creation of novel or enhanced metabolic pathways in organisms never before possessing such traits.

Biotechnologies Applicable to Biofuels.

  • Classical mutation and selection or plant breeding: this encompasses a variety of well-known, decades-old techniques for selectively breeding or otherwise selecting naturally-occurring (or mutationally induced) variants of a starting strain or plant variety.
  • Recombinant DNA: insertion and expression of heterologous genes into a desired host organism (microorganism, algae or plant) to improve a desired trait or biochemical function in the host organism.
  • Directed evolution: this technique generally involves growing a desired microbial strain under certain limiting conditions that impose selective pressure under which those mutant overperforming strains that arise can eventually outcompete the starting strain.
  • DNA shuffling: this is a form of directed evolution where the gene encoding the enzyme targeted for improvement is mutated in millions of permutations using recombinant techniques, followed by selection and isolation of superior performers, often carried out in multiple iterations of selection.
  • Metabolic engineering: this term refers to the use of recombinant DNA technologies to create new metabolic or biosynthetic pathways in host organisms, or to enhance existing pathways, through the engineered, coordinated expression of several heterologous or enhanced enzymes in the desired pathway.
  • Synthetic biology: in this technique biochemical pathways or even entire microorganisms are created “from scratch”, to create pathways or organisms not previously found in nature. It can be viewed as a more ambitious approach to metabolic engineering, as it often involves creation of biochemical pathways never before existing in the host organism of choice.

The entries that will follow over the next several days will provide overviews of the approaches that are being taken to modify microorganisms, algae and plants to improve biofuel production. Following that, I’ll begin to review the companies that are active in using advanced biotechnology in the different sectors of the biofuel industry. Please contact me with any questions you may have.

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 www.slideshare.net/djglass99.

Biotechnology and Biofuel Production

Welcome to the Advanced Biotechnology for Biofuels blog. This blog will discuss new developments relating to the use of genetic engineering and other techniques of advanced biotechnology for biofuels applications. More specifically, I’ll look at the many activities taking place around the world in the private sector and academia directed at the development and use of genetically engineered or other modified organisms for production of ethanol, biodiesel or other transportation fuels like butanol and isobutanol. These activities are so diverse and so widespread, and the field changing so rapidly, that it is nearly impossible for any report to be comprehensive and completely up to date, but I will try my best to discuss as much relevant information as possible in an attempt to be comprehensive. 

Much of the discussion here will focus on the commercial sector. The companies I’ll profile in this blog are primarily those that are using recombinant DNA genetic engineering or other advanced biotechnologies (e.g. synthetic biology, directed evolution, metabolic engineering) to improve or create specific strains of microorganisms, algae or plants for use in biofuels processes. But frankly, there are now so many ways in which microorganisms and plants can be improved using either “traditional” techniques of mutagenesis or cross-breeding or more “innovative” techniques within the rubric of biotechnology, that the lines can get quite blurry between one technology and another. So, some of the companies to be profiled are not using “genetic engineering” per se at all, or in other cases are using such techniques only in their internal research but their commercially-utilized strains are not genetically modified. I’ll try to make this distinction explicit in the installments to come. 

A large number of companies in the U.S. and elsewhere are conducting R&D using advanced biotechnology to bring about improvements in the commercial production of ethanol, biodiesel and other biofuels. In this blog, I’ll tend to focus on companies that are all in the category one can call “technology providers”, specifically biological technology providers.  What do I mean by this? I use the term to distinguish these companies from the many others that have sprung up in recent years for the commercial production of biofuels. The emerging industrial sector devoted to the production of ethanol and other biofuels includes companies across the whole spectrum of activities from growing, harvesting and selling the biomass that is used to produce the fuel (the “feedstocks”), to operating the conversion process (which may use biological, chemical, or physical means of transformation), to separating and purifying the fuel, and finally storing, selling and transporting the fuel. The companies I’ll discuss in this blog are all creating or developing improvements in one of two particular phases of the production process: either improving the cellulosic or leafy plants or other vegetative material that are the most common feedstocks for fuel production, or improving the microorganisms, algae or enzymes that help catalyze the biological transformation of biomass to fuel (or in the case of algae, converting sunlight and carbon dioxide to fuel). It’s certainly true that the biofuels industry includes technology developers other than those profiled here, particularly including companies developing chemical or physical catalytic methods or other types of process improvements for use at various points in the production chain, but my focus will solely be on improved biological technologies. But it’s also true that many of the “technology providers” in this category are also developing technological improvements in downstream processing, further blurring the lines between different categories of companies. 

I will also try to observe a further distinction among the biological technology providers. Ethanol, biodiesel and other fuels can be produced without the use of advanced technology, utilizing many types of organic biomass not having any special properties (notably including waste materials of many kinds) and utilizing naturally-occurring, non-selected varieties of microorganisms as the catalyst. For the most part I will not be discussing those companies in the biofuels business that are using or selling nonproprietary (i.e., generic) components, and I’ll instead focus on those companies that are using or developing proprietary compositions, methods and techniques using genetic engineering or other advanced biotechnology. However, this is not a bright line distinction: some of the companies to be profiled, particularly in the algae sector, are using microbial strains as biofuel catalysts that are proprietary, but which are naturally occurring  or in some cases selected or enhanced using traditional techniques rather than genetic engineering. With regard to the microorganism and algae companies, I’ll generally include a company if the organism central to its commercial process is genetically modified, selected or enhanced in any way, or is otherwise “proprietary” to the company. However, for the companies focusing on development of novel plant feedstocks, I plan only to include those that are improving the plants through biotechnology, or at least are using biotech methods in their research (e.g. as a tool to enhance breeding efforts) and I won’t be including companies that are simply growing improved, but traditionally-developed, cultivars of known feedstock crops. 

In addition to describing the lay of the land within the industry with company profiles, I’ll touch on several other important topics for the commercial use of advanced biotech for biofuels. I’ll discuss and highlight promising research and inventions arising from academic institutions, government labs, and other non-profit institutions, and will hopefully be able to highlight technologies that might be available for licensing. I’ll examine some of the innovative strategies that companies are taking to gain a competitive edge, such as integrating proprietary biofuel production processes with downstream process improvements, or by coproduction of “green” chemicals. I will also try to discuss the economic factors affecting the use of genetic engineering in biofuel production and assess the prospects that advanced biotechnologies will play a significant role in the biofuel industry in the coming years.

 I’ll also spend some time discussing the impact of biotechnology-specific laws and regulations on the uses of genetic engineering and other biotech methods in biofuel production. This is a longstanding interest of mine, with experience and expertise in dealing with U.S. government regulatory agencies going back to the earliest days of the biotech industry in the 1980s (http://dglassassociates.com/REGUL/biofuels.htm). Commercial uses of engineered or modified organisms for biofuel production may be affected by the biotechnology regulatory framework that exists in the United States and other countries. There has been a widespread perception that these regulations are prohibitive to deal with or that compliance is necessarily time-consuming and costly – I hope I will be able to dispel these misconceptions, and show that for most projects involving engineered organisms, regulatory approval should be straightforward and not difficult to obtain. 

So, I hope you find this blog to be informative, and that you follow it and the installments to come. Please feel free to add your comments or to contact me with any questions you may have. 

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 www.slideshare.net/djglass99.