Ottesen was working at the Carlsberg Research Laboratory under the chemist Kaj Ulrik Linderstrøm-Lang (1896–1959), who during the post-war years turned the lab into an international centre of modern biochemistry.

Linderstrøm-Lang had developed new methods for understanding how proteins fold and how their structure is related to their function. Ottesen continued this research as Linderstrøm-Lang’s successor as head of the lab from 1959 to 1987 but took it in a new direction. Instead of studying protein structure and dynamics, he wanted to understand how proteins change over time.

In experiments with ovalbumin, the main protein of egg white, Ottesen noticed that the crystals changed shape over time, as flat plate-shaped crystals replaced the usual needle-shaped ones. He discovered that the change was caused by bacterial degradation, which produces an enzyme that cleaves off seven amino acids from one end of the protein.

The new protein was named plakalbumin. The discovery showed that enzymes can alter proteins in a precise and targeted way, rather than simply degrading them. This process, known as limited proteolysis, was key to the understanding of how proteins are activated and regulated in living organisms. It showed that proteins are not fixed structures but dynamic molecules capable of changing form and function depending on the cell’s needs.

The enzyme that had cleaved off the seven amino acids and thus formed plakalbumin was found to stem from the bacterium Bacillus subtilis. Together with his mentor, Linderstrøm-Lang, Ottesen named the enzyme subtilisin in 1947, referencing the bacterium where it was first discovered. Later, additional enzyme variants were found, including subtilisin Carlsberg, named after the Carlsberg Research Laboratory. Further research showed that in addition to causing specific changes to the structure of certain proteins – a process that in nature plays a key role in the regulation of biological functions – the subtilisin enzyme could also destroy them entirely.

Subtilisin proved to be stable and well suited for industrial manufacturing. When Ottesen sent a sample to the Novo Terapeutisk Laboratorium, it marked the beginning of the development of enzyme-based laundry detergents. The discovery laid the foundation for the Danish enzyme industry, which has since reached an international scale, with Novo (now Novonesis) as a leading player.

Continuing his studies of protein structures and enzyme functions, Ottesen demonstrated that tiny changes in the chains of amino acids that make up proteins can have major consequences for their shape and activity. This had implications far beyond the laboratory, ranging from our understanding of the body’s own digestive enzymes to the development of new biotechnological methodologies.

He also developed high-precision measuring methods and instruments for biochemical research. In collaboration with the Danish company Radiometer, he created the so-called pH-stat device, which made it possible to study certain enzyme reactions under controlled conditions, and which became standard lab equipment around the world.

Ottesen’s research formed a link between basic science and practical applications. Based on an egg-white protein in the lab, he cultivated new knowledge with implications for both research and industry and demonstrated that precision and curiosity can generate results that reach far beyond the world of science. 

The chapter is written by Asser Pelle.