Finding and producing enzymes

Learn how we select the right enzyme to do the right job by using modern biotechnology.

Finding a multitude of enzymes

It may be that the perfect enzyme is not in the library. If this is the case, soil samples, sometimes from very exotic locations around the world, must be examined to find the right microorganism with the capability of producing the enzyme that can remove the stain on the shirt. The starting point depends on the customer's requirement. If the enzyme needs to function under very hot conditions, our researchers in hot-spring areas are the natural first port-of-call. Collecting the soil samples is the easy part, but one gram of soil contains more than 4,000 different microorganisms, each of which can produce hundreds or thousands of different enzymes! Using the biggest toolbox of screening technologies in the world, Novozymes' scientists can easily find microorganisms which are potential candidates for producing the right enzyme. This is one of the things that makes Novozymes a unique company.

Selecting the right enzyme

In the laboratory, our scientists start searching the many candidates collected in the wild for a microorganism which can produce the desired enzyme. Novozymes has several methods for finding the right bacterium or fungus.Normally the scientists grow the selected microorganisms in a variety of different conditions and media, narrowing down the number of suitable enzymes. The search for the right enzyme is a highly automated process. Huge robotic systems can simultaneously test a culture of microorganisms on 12 different substrates such as starch, proteins or fats. With the help of the robots, Novozymes' researchers can scan thousands of microorganisms in just a few days. The final test involves scanning the enzymes under the precise working conditions in which that enzyme will be used in the final product. The scientists can then be sure that they have found the microorganism capable of producing an enzyme to do the job.

Finding the gene that makes the enzyme

Having found the perfect enzyme for the job, our scientists are now ready to find the gene that instructs the microorganism to produce the enzyme. Like human beings, microorganisms are able to produce hundreds of different enzymes for solving all kinds of problem. But we are only interested in a single enzyme; the others might produce unwanted side-effects. Finding the genetic code for the right enzyme is what really sets our experts apart from normal scientists. Novozymes has the world's biggest toolbox of biotech-based screening technologies, together with some of the best scientists in the business, for finding and recreating the exact genetic code of the desired enzyme. And once the genetic code has been isolated, the researchers can improve the enzyme even further in many different ways.

Transferring the gene to our production organisms

Often the original microorganisms are not the best for producing the enzyme in large-scale production. They may not produce much enzyme or might be hard to grow in large numbers. Sometimes the original microorganism also produces a large number of other substances which might be dangerous to humans. In order to produce the enzyme in large quantities and without having to worry about the by-products, we combine the best of the original microorganism with Novozymes' own safe and fast- growing production microorganisms. The gene from the original microorganism that codes for the enzyme is inserted into the production microorganism using modern biotechnology. Our microorganisms are then able to produce exactly the same enzyme, but in larger quantities and under much safer conditions than the original microorganism.

Developing the production method

Before we start large-scale production of the enzyme, the exact living conditions for the production organism must be determined. Even though we know our microorganisms very well, numerous tests still have to be carried out. The microorganisms feed on nutrients derived from e.g. maize (corn), soy beans, potatoes or sugars. But the right nutrients for the microorganisms depend on the enzyme which is to be produced. The same applies to the temperature, oxygen level and pH to which the microorganisms are exposed. In order to get the most efficient production, our scientists must create the right environment for the microorganisms to work to their optimum capacity.

Making microorganisms produce enzymes

Microorganisms, not larger than 1.5 micrometres, are the heart of Novozymes' business. A single bacterium or fungus is able to produce only a microscopic portion of the enzyme needed. A billion microorganisms, however, can produce the amount of enzyme that makes the business feasible. The process of multiplying microorganisms by millions is called fermentation. By means of simple cell division, more and more organisms appear, all producing the enzymes which we desire.In the laboratory, a very small amount of selected microorganisms that can produce the desired enzyme is grown in a small-scale fermentation tank to get the fermentation started. Once everything is up and running, it is time to let the microorganisms grow to the best of their ability in our three-storey fermentation tanks. Everything in the tank is controlled, with nutrient quantity, temperature, pH and airflow comprising the main parameters in the process. With more than 50 years' experience, Novozymes has developed the fermentation process to perfection.

Recovering enzymes from the fermentation broth

When fermentation is complete, the fermentation tank is full of one huge mix of unused nutrients, water, microorganisms and valuable enzyme. The enzymes are separated from the rest of the liquid in a large drum-filter. The filter is coated with a thick layer of wax that allows the water and enzymes to penetrate, whilst the nutrients and microorganisms are caught in the sticky surface of the wax. As the drum-filter rotates, the fermentation liquid is sprayed on. The water and enzymes are sucked into the middle of the drum, leaving the nutrients and microorganisms on the surface of the wax. A large knife then slices the wax, nutrients and microorganisms away. Following a series of other filtration processes, the enzymes are finally separated from the water using a simple evaporation process.

Using surplus material as fertilizer

Many industries have problems with waste products.Novozymes doesn't! Dealing with nature's own technology, our waste is actually beneficial to the surrounding environment: it is used as fertilizer on local farms.Firstly, we make sure that no living or intact microorganisms leave the production plant by treating the mix of wax, nutrients and microorganisms with heat and chalk. The microorganisms in the treated fermentation waste are then ready for their final contribution to a sustainable industrial solution. The waste is used as a top-grade fertilizer on the fields of the farms surrounding the production plants, thus promoting the growth of yet another natural product, crops.


Delivering the final product

Once the enzymes have been formulated as either liquid or granulate, they are packed in cans or bags and are then ready to leave the factory. With factories on four continents, Novozymes is always nearby. But even when the enzyme products have left our factory Novozymes continues to work for its customers, who are often developing a brand new product which might require expert assistance. Novozymes is the number one expert on enzymes and how to handle, formulate, produce and use them. Service is therefore our second-largest product and the Tech Service department even works free of charge.