Biocatalysis

The Journal Chem. Comm. just designated a scientific paper by Nicholas Turner, Matthew Truppo, and J. David Rozzell (Hey, that’s me!) as a Hot Article.  The communication describes a two-enzyme system for producing enantiomerically-pure amines, something which is difficult to do by other means. The link is here. The reaction sheme is below for those chemically inclined.

OK, I know it’s a shameless plug.

Formed through a merger of San Diego-based Diversa Corporation and Cambridge, MA-based Cellunol a couple of years ago, Verenium has set cellulose-derived ethanol production as its major goal. The company still maintains a small but growing industrial enzyme business operated out of San Diego and has extensive technology and state-of-the-art know-how in the genetic engineering and optimization of enzymes, but for today’s Verenium, future success appears firmly hitched to the fuel ethanol wagon.  Having British Petroleum as a major funding partner doesn’t hurt. BP made a 90 million investment last year to help Verenium finance its development and commissioning of its Jennings, LA demonstration plant.  Just last month (Feb. 2009), Verenium and BP formed a 50-50 joint venture to commercialize cellulosic ethanol from no-food feedstocks. The first commercial plant is planned for Highlands County, Florida, with groundbreaking set for 2010. As for technology, Verenium uses classical pre-treatment technology along with enzyme treatment for converting cellulosic waste such as bagasse to fermentable sugars, which are then converted to ethanol.

The Jennings and Florida plants better just be a start. Revenues from those plants will not even come close to bringing the company to breakeven, let alone profitability. As long as BP supports the company, Verenium will have some staying power. And since the industrial enzymes business is not a good fit with an ethanol producer, look for enzyme business to be spun off or separated at some point.

Royal Dutch Shell announced today (March 10) that it was expanding its collaboration with Codexis to use Codexis’ shuffling technology to develop improved enzymes and microbes for producing biofuels from non-food raw materials. Shell already has a close cooperation with Canadian ethanol producer Iogen. Today’s announcement focuses on using the Codexis technology to both enhance the conversion of cellulosic materials to ethanol in the Iogen process and develop additional biofuels “similar to gasoline and diesel.” Shell will also increase its equity stake in Codexis and take an additional seat on the board. Read the full article here. We will take a closer look at these companies in upcoming biofuels company profiles.

UK-based companies Cambridge Major Laboratories and Novacta Biosystems announced a collaboration to develop a range of process development, custom synthesis and biocatalysis offerings for the pharmaceutical industry. Novacta will bring its know-how in biocatalysis and metabolite synthesis and Cambridge Major will scale-up for commercial applications. The two companies are clearly hoping that adding biocatalysis to the portfolio of offerings from Cambridge Major will broaden the overall appeal by broadening the capabilities to include biocatalytic solutions. 

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

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.

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.