Biocatalysis

The Applied Biocatalysis Center at based at the Technical University of Graz, Austria maintains one of the largest research efforts directed toward biocatalysis. Funded as a Competence Center (Kompetenzzentrum), or K+ Center in Austria, the research efforts have already resulted in a number of biocatalysis successes. DSM, in particular has funded significant projects, including work to clone, express and optimize hydroxynitrile lyase enzymes for chiral cyanohydrin synthesis, and the cloning and first successful expression of pig liver esterase in commercially significant amounts. The Center also maintains a good web site: A-B Graz

There is so much conflicting information about the cost of bio-ethanol that it is not surprising to have widespread confusion about whether its production makes economic sense. Here are some numbers to think about.

Ethanol has only about 60% the fuel value of gasoline; thus, based on energy content measurements, we need about 1.6 gallons of ethanol to equate to one gallon of gasoline on an energy conversion basis. Based on current production methods, the cost of the amount of glucose to produce 1 gallon of ethanol is about $0.80-1.00. Adding costs to isolate and refine the ethanol, the overall cost rises to about $1.40/gallon, which after adjusting for the lower fuel value translates to about $2.24 per gallon equivalent of gasoline, and a bit higher cost once it gets to the pump. Improvements will be made, but ethanol is not yet on an economic par with petroleum-derived gasoline as a transportation fuel. Ethanol does, however, place an upward limit on what gasoline can cost as long as ethanol is readily available to substitute for gasoline. Regardless of what the ethanol producers claim, I would estimate that, realistically, ethanol can be competitive only when gasoline is at or above $2.50 per gallon at the gas station.

Drug cancellations are the bane of the existence of biocatalysis developers. A nicely selective, efficient enzymatic process is developed, tested, and just as commercialization seems at hand, the drug gets pulled. Pfizer just announced such a cancellation for esreboxetine. Two chiral centers down the drain.

What is indisputable is that every gallon of biofuels generated replaces roughly a gallon of fuel that would otherwise come from petroleum (the equation is not exact due to the varying energy value of different biofuels). This both reduces our dependence on foreign oil and extends our domestic oil supply. Economics are another matter. Biofuels cannot compete with petroleum at today’s (February 2009 when this was written) oil prices of less than $40 per barrel. But biofuels do help set a cap on the price oil. What that price level is remains a subject for debate and varies from one biofuel to another. Delving into the details of the cost of biofuels is a topic we will address another time. It is important, however, to acknowledge that the capping effect on fuel prices exists as long as biofuels are maintained as a viable alternative. 

Typically, the term biofuels means transportation fuels. This is worth remembering because biological materials that include ethanol, vegetable oils, and animal fats have been used for centuries for cooking and lighting (think of alcohol burners, old-fashioned street lamps, candles). But today, almost no one is thinking about using biofuels for anything other than powering internal combustion engines (The idea is not a novel as it sounds; Henry Ford originally designed the Ford Model T to run on ethanol, not gasoline).

Currently there are two biofuels available in large enough quantities to have an impact on fuel consumption: bio-ethanol and biodiesel.  Bio-ethanol is essentially the same substance humans have been producing for 6000 years in beverages by fermenting sugars present in almost any starchy vegetable or sugary fruit. The main difference is the refining needed following distillation to produce ethanol to the substantial exclusion of water. Only then can it burn efficiently in a truck or automobile.

Biodiesel is completely different, chemically. It is produced by reacting plant or animal fats with methanol to produce long-chain fatty acid methyl esters, which can be blended in substantial amounts with traditional petroleum-derived diesel and used as a transportation fuel. Biodiesel is, in point of fact, a good fuel, and it is cleaner-burning than traditional diesel. On some farms all the tractors and farm equipment are run on 100% biodiesel. 

There are other biofuels–butanol and hydrocarbons, for example– in intense development. How good are these various bioifuels? Stay tuned, more information is forthcoming.

There is a steady buzz in the media about biofuels, and there are some strong opinions about this topic. At one extreme are people who believe that biofuels will save the world from a dependence on petroleum and stave off global warming. On the other side are those who think that biofuels are uneconomic and nothing more than the latest government-subsidized boondoggle. What is the real story? No one post can cover the topic comprehensively, but we are starting a series on biofuels that will go into detail about the biofuels products, the pros and cons of producing them,  and the leading companies in the field. Please register and comment; your feedback will be most welcome.

Ever wished you could find out how a compound could be degraded or biosynthesized? A great resource to help answer this questions is the U of  Minnesota Biocatalysis/Biodegradation Database, compiled and regularly updated by Prof. Larry Wackett and colleagues. IT contains 182 pathways, 1269 reactions, 177 compounds, 821 enzymes, 479 microorganism entries, and more. This is a great resource, and we will include it in our growing list of resources and link to it here.

Green chemistry and industrial biotechnology has penetrated a new market. De-icing fluid maker Kilfrost is incorporating 1,3-propanediol, produced by Loudon, TN-based DuPont Tate & Lyle Bio Products, into a new line of aircraft deicers. According to the manufacturer, the new de-icing fluid has “serious green credentials” and outperforms existing de-icers. Current de-icing products are based on propylene glycol. This product marks an important breakthrough for biocatalysis and industrial biotechnology. I expect to be able to report on an increasing number of biotech-based green chemistry products in the future as biocatalysis becomes a more mainstream technology.

It is important to point out that biocatalysis is not a panacea, and I say this as an evangelist for biocatalysis. There are both pros and cons for the use of biocatalysis as compared to more traditional chemical catalysis. As a catalyst, a biocatalyst does what any catalyst can do: increases the rate at which a chemical reaction takes place, but does not affect the thermodynamics of the reaction. To take maximum advantage of biocatalysis, we need to understand what biocatalysts do well, and equally what they do poorly, and then seek to implement biocatalysts in processes that benefit from their advantages.

One of the most important advantages of biocatalysts is high selectivity, manifested as stereo-selectivity (for chiral synthesis or separation, often used for the synthesis of pharmaceutical intermediates in which only one stereoisomer possessesthe desired biological activity), positional selectivity (also known as regio-selectivity, allowing selective modification of a specific site in a molecule), and functional group selectivity (i.e. chemo-selectivity, allowing one type of chemical functional group to be modified in the presence of another, sometimes more reactive functional group). Such selectivity is highly desirable in chemical synthesis, offering benefits such as higher yields, fewer side reactions, elimination of protection and de-protection steps, purer products, easier recovery and separation, and reduced environmental waste. There are also operational advantages, including the ability to carry out reactions under mild operational conditions, avoiding extremes of pH, temperature, and pressure that often require the use of expensive equipment or energy intensive processing. Biocatalytic processes also rely on catalysts that are biodegradable and are produced from renewable resources, meaning the processes are typically “greener” and more sustainable. Since there is an enzymatic counterpart to most known chemical reactions, the potential scope for the application of biocatalysis is broad.

Practically speaking, however, this breadth of scope in the chemical industry has not been realized. Presently, I estimate that well over 100 different biocatalytic processes are implemented in pharmaceutical, chemical, agricultural, and food industries, which may at first glance seem considerable. However, this represents only a small fraction of the processes developed and carried out currently. Enzymes have not yet been developed to cover as broad a spectrum of chemical reactions as have chemo-catalysts. Researchers in both academia and companies are working to overcome this limitation, but it will take time. Speed of process development is also often slower for biocatalytic processes than their chemical counterparts, in part due to the lack of experience that chemists have with the use of enzymes and microbial cells. Modern biotechnological tools now allow enzymes to be significantly improved—optimized—for a desired reaction, but this optimization is often too costly and time-consuming to meet tight timelines; therefore, broad application remains elusive. By focusing on those reactions where enzymatic alternatives are relatively well-developed now, honing our expertise in using biocatalysis, and staying abreast of future developments that will bring a wider range of practical biocatalytic alternatives, we can choose wisely where to invest resources to maximize the value of this rapidly developing technology. 

A good place to start is with definitions, to provide clarity about our subject.

Biocatalysis can be defined as the use of natural substances, which can be one or more enzymes or cells, living, dormant, or dead, to catalyze a chemical reaction or series of chemical reactions. Thus, biocatalysis includes the one-step enzymatic conversion of fumarate to aspartic acid (a component of the non-caloric sweetener aspartame), the two-step oxidation of ethanol to acetic acid (vinegar can be made this way), and the multi-step brewing of beer (quite likely the oldest example of biocatalysis, with historical records dating back 6000 years!).

A biocatalyst, then, is a natural substance, being an enzyme, cell, or a group of enzymes or cells catalyzing a chemical reaction or series of chemical reactions.

As we add content to this site, we will focus on the biocatalyst products available, their applications, their advantages, and the sources of those biocatalyst products, which may be both companies and academic institutions. We might even get opinionated!