A history of technological innovation

Audited by PwC

In our quest to deliver more from less, Novozymes invests heavily in technological innovation to improve both the strains that produce our enzymes and the performance of the enzymes themselves.

Novozymes is a growth company with a difference. Rather than simply building new factories to accommodate rising sales volumes, we use biotechnology to increase output from existing facilities and reduce consumption of raw materials, water, and energy. This benefits both Novozymes and the environment, as we are able to produce more from less.

Continuous efficiency improvements have ensured that the construction of new production capacity has lagged growth in sales volumes, and will continue to do so in the future. The technological innovation that makes this possible also plays an important part in the discovery and development of new enzymes.

Continuous improvements

Novozymes has produced enzymes by microbial fermentation for more than 50 years, first as part of Novo Nordisk and since 2000 as an independent company. The first genetically modified (recombinant) production strain was launched in 1988, and our product portfolio is now dominated by enzymes from recombinant microorganisms.

Enzymes are produced by microorganisms such as bacteria, fungi, and yeasts throughout nature. To produce enzymes on an industrial scale, however, we have to stimulate and improve the microorganisms so that they yield more of the desired enzyme, release fewer unwanted by-products, and generally perform better and more efficiently in the production environment.

This is an ongoing process, and we are constantly developing new technologies that push the boundaries of productivity. Increased understanding of the biology of the microorganisms that we work with has dramatically accelerated this process. Twenty years ago, even minor modifications of our production organisms could take a team of scientists several months or even years. Today, a single scientist can design and implement significant genetic modifications in just a few weeks – and with a much more predictable outcome. Ten years ago, the genome sequences of our strains were largely unknown. Today, sequencing an entire genome is standard procedure.

Once developed, a new production strain opens up new possibilities in our production processes. A constant focus on optimizing our processes to get the most out of each individual strain, while at the same time retaining a fairly standardized production setup, enables significant further improvements. We also make great efforts to find cheaper raw materials and minimize energy and water consumption.

State-of-the-art technologies

Novozymes strives constantly to improve the properties of our enzymes. An enzyme is a protein consisting of a string of amino acids, and it is the sequence and positioning of these amino acids that determine the enzyme’s properties, such as stability and activity. By using our technologies to make our enzymes longer lasting or more powerful, we can lower the dosage of enzyme required in customers’ applications.

One of the techniques is crystal structures showing how all the components of the enzyme molecule are positioned in 3D, enabling us to modify the amino acid composition of an enzyme. Using computer programs that simulate the function of the enzyme, we get ideas for how the amino acid composition can be modified to improve the enzyme’s performance. These ideas must then be tested. In the best case, we only need to test hundreds of enzymes with different combinations of modifications to get the desired result. Often, however, the task is so complicated that we have to spend months testing hundreds of thousands of modified enzymes. In this case, robotic equipment is used to carry out high-throughput screening to find the “needle in the haystack.” This is only possible thanks to the advances in robotics over the past 20 years. Novozymes has exploited the potential of this technology from its very infancy and has in many cases developed in-house robotic solutions. 

Other technological developments have also helped transform our work on optimizing enzymes. Twenty years ago, only a few protein 3D structures were known, and very few tools were available for exploring the function and dynamics of these structures. Today, much more structural information is available, and general understanding of enzyme function has greatly improved. Computer power has increased enormously, enabling the use of new simulation techniques such as molecular dynamics to help understand the determinants of enzyme stability and activity.

New technologies are constantly improving our understanding of enzyme molecules and ways of working with DNA, making optimization increasingly efficient. Of course, these technologies are only as good as those who use them, which only serves to emphasize the need for highly talented people. Human creativity and interaction have always been, and will always be, the key to our ability to innovate.

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“It’s a matter of jointly - with our customers - developing and solving those needs and ideas they come up with.”
Per Falholt, Research & Development