Why Use Biocatalysis?

If you think about all the desirable features in a catalyst, your list would probably look something like the one below.

Characteristics of the ideal catalyst

High turnover number

Cost-effective

Chemo-selective

Stereoselective (when necessary)

Sustainably produced

Non-toxic

Biodegradable

Broadly useful

Enzymes—at least the right enzymes—can meet all of these requirements. Enzymes are proteins, sometimes with prosthetic groups, sugars or lipids bound to them. As such they are completely natural and biodegradable. Typically produced by microbial fermentation from inexpensive sugars as starting materials, enzymes are sustainably produced. Enzymes typically have high turnover numbers, and when produced efficiently by modern genetic engineering methods, enzymes are highly cost-effective. They are also broadly useful, catalyzing reactions with almost every type of chemical compound and functional group, and being catalytically active in the presence of water as well as various organic solvents.

As selective catalysts, both chemo-selective and stereoselective, enzymes are often unequalled. Two examples illustrate the selectivity advantages of a biocatalyst. The first example, nitrilase, is an enzyme that chemo-selectively hydrolyzes a nitrile to a carboxylic acid. The enzyme catalyzes this reaction at neutral pH and room temperature. Compared to chemo-catalysis that requires acid or base, often combined with elevated temperatures, a nitrilase has clear advantages in avoiding the inevitable side reaction that occur when a multi-functional compound is expose to strong acid or base. In fact, a nitrilase can hydrolyze a nitrile cleanly and selectively in the presence of an ester. Try developing a chemo-catalyst that can accomplish that!

In terms of stereoselectivity, there are many examples. I will just cite ketoreductases as a representative one. A well-designed ketoreductase can catalyze the reduction of a ketone to a chiral alcohol with 100% stereoselectivity. I have seen several cases where the undesired stereoisomer could not even be detected in the crude product stream. That claim can be made about few chemo-catalysts for ketone reduction.

Then there is the ability to use the tools of genetic engineering to improve the fitness of an enzyme for almost any application.  Often called directed evolution, various methods are now available to change the amino acid sequence of an enzyme to make it more stable, more active, and more selective. Enzymes can be engineered in this way to work well in the presence of organic solvents, higher temperature, different levels of acidity and basicity. The new enzymes that are created by directed evolution are novel compositions of matter, and therefore patentable, providing IP protection for the developer.

Enzymatic processes are also inherently green and sustainable, broadening the appeal of using biocatalysis. And no longer are enzymes relegated to a few small-volume, high-value opportunities. Large volume applications are being increasingly looked at by many researchers as the cost contribution of biocatalysts comes down due to lower enzyme production costs and better engineered enzymes that provide greater turn-over numbers.

The Enzyme Sources page provides a comprehensive world-wide listing of companies that offer enzymes for biocatalysis applications. It is updated regularly in an effort to always provide the most current and useful information  on biocatalysis sources and resources. Many companies offering enzymes for biocatalysis are small entities. However, it is important to keep in mind that most companies developing enzymes for biocatalysis applications will outsource the large-scale production of enzyme to a toll fermentation provider. Thus, even companies without large-scale manufacturing facilities are often able to offer bulk supply when needed to support a scaled-up process.