Biological production of industrial basic substances

Industrial basic substances for plastics or medicines are often produced using crude oil, even though there are biological alternatives. However, these options are generally more expensive or have their own set of problems. At the Karlsruhe Institute of Technology (KIT), Dr. Theo Peschke and Dr. Kersten S. Rabe under the direction of Professor Christof M. Niemeyer at the Institute of Biological Interfaces study a new biocatalytic material that facilitates the production of various chemicals.

Dr. Peschke, Dr. Rabe, biological processes with enzymes have been around for a while. Why does the industry sector not apply them more frequently??

Dr. Theo Peschke: Enzymes have enormous catalytic power and have been continuously advanced by nature through evolution. There is extensive academic research on enzymes and they are thus already being used in various areas of research. They facilitate many different reactions and could theoretically also be used by the chemical and pharmaceutical industry.

Dr. Kersten S. Rabe: The issue is that very few enzymes can be formed via conventional methods to where they can be used in a variety of industries. That’s because enzymes can often not be attached in their active state. This means that it is difficult to bind them to a solid surface without damaging them.

Peschke: That’s also why previous industrial uses focus on just a few very stable enzymes. That’s a pity since nature has so much more to offer.

What are the current uses of enzymes?

Rabe: There are very well-established fermentation processes that use living cells to generate amino acids or vitamins for example. Having said that, these are processes that are best suited for very simple and only a specific class of substances.

What is your approach?

Rabe: Our study focuses on working with clean enzymes. That means they have been purified to where the cell has been removed. This is labor-intensive but we continuously apply this during the process, so the work pays off. What’s more, you can avoid undesirable side reactions caused by cell remnants. This makes it different from conventional biological processes, which are basically well-established, though not for complex chemical reactions that necessitate several reaction steps. We have succeeded in developing a material solely from pure enzymes.

Peschke: There are actually methods that achieve an anchoring of the enzymes on a surface. The problem there is that the surface in a reactor is always limited. You previously had to introduce particles or polymer carrier materials to fix the enzymes in the reactor or tube. That's why we linked the enzymes directly together. This eliminates the need for expensive carrier materials. By eliminating these support materials, we achieve a higher enzyme density, resulting in a far more efficient process. What’s more, we have changed the enzymes to prompt them to self-assemble. That’s why we no longer need a chemical cross connector for the reaction. In the past, only very stable enzymes could withstand this conventional process without loss of activity. Now we are able to work with brand-new enzymes and biological reactions.

Rabe: This is similar to a two-component adhesive. The enzymes form a gel-type material when you mix them. In the reactor, they help convert the basic substances into the end product.

How big is a reactor?

Peschke: The size of our current prototypes here at the Institute of Professor Niemeyer is about 7.5 cm x 2.5 cm with a volume of 150 microliters. They are very tiny but you can essential apply this to other dimensions.

What dimensions would you need to facilitate industrial use?

Peschke: It depends on how much product you have to generate. Some methods have shown that you can easily batch several of these reactors in parallel. In other words, instead of entirely new complex process calculations with a larger reactor, you just increase the number of microreactors. This is called parallelization. You use linear extrapolation of the process and subsequently obtain the needed dimension.

Rabe: In the industrial sector, parallelization of reaction units in pure chemical syntheses is quite common. However, it was previously impossible to do this with biological catalysts because you could not get them into a form that allows them to be continuously active in the flow reactor. Our method shows that you can operate the reactor with enzymes for weeks.

Does this mean that the technology to use your procedure is already available?

Rabe: Yes, the technology is available and there is also interest in using enzymes.

Peschke: We take several industry developments like microreactor technology into account in this setting. Several processes have shown that it is better to take a small reactor and connect several of them in parallel. This facilitates more controlled reaction conditions because microreactors enable more effective heat transfer and better mass transport. That’s also why some industrial processes are now conducted with microreactors. Another thought was that large-scale factories are not necessary to produce specialty chemicals that don’t require mass production. Portable factories are a conceivable option in the form of containers for example.  In this case, you could connect multiple reactors, allowing you to set up the container where the material is needed. This facilitates on-site production and eliminates large-scale facilities in one place that supply the global market.

Rabe: Chemicals that are produced on a mass scale will not be produced in these types of reactors anytime soon. That’s because crude oil is unfortunately still unrivaled in this setting. Having said that, the process is suitable for plastic building blocks, medication or cosmetics that involve multiple reactions or a fairly complex synthesis. In a manner of speaking, you front-load the basic materials, processes subsequently take place inside the successively connected reactors and out comes the desired product.

In which area does medical technology benefit from your development?

Peschke: It is certainly feasible to produce biomaterials using antibodies or other relevant proteins and develop rapid diagnostic tests or lab-on-a-chip systems for example. That said, in the foreseeable future, the process will still be rather costly for larger quantities of plastic because the traditional synthesis methods are much more cost-effective by comparison. Though in theory, it’s still a feasible option.

What are your next steps?

Rabe: We will continue to pursue this subject matter and increase its productivity and efficiency in the future. We will continue to study the geometry of the reactors and the material composition or how fast we pump the basic substances through the reactor. Most notably, we aim to produce the material with other industrially important enzymes. These are all issues we didn’t address in-depth in our first publication. Needless to say, together with Professor Niemeyer, we are also considering commercializing this technology.