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.

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.