‘In the ‘80s we at DSM felt that antibiotics should be synthesised differently. Although at that time, we did not produce those medicines ourselves.’ Says Alle Bruggink, former Nijmegen professor, former head of DSM Chem
‘In the ‘80s we at DSM felt that antibiotics should be synthesised differently. Although at that time, we did not produce those medicines ourselves.’ Says Alle Bruggink, former Nijmegen professor, former head of DSM Chemfern Research, and member of the Dutch EL&I Ministry’s Scientific and Technological Committee on the biobased economy.
‘Antibiotics form a group of complex substances. They need many organic chemical steps for their synthesis, and then, production costs were too high. Third world countries which first bought antibiotics in Europe, started to produce them themselves, and did so at lower cost. There was a solution, biocatalysis, which allows many reactions to take place along a shorter pathway, using enzymes. Antibiotics are peptides, consisting of coupled amino acids. The protease enzyme separates peptides, and we thought it might be possible to reverse that reaction in order to remove the side chain from the penicillin ring, and mount another. Gist-brocades in Delft started research along these lines and had its first successful lab tests around 1990. They did not merely process the side chain, but also the ring. They succeeded in changing the penicillin ring containing five atoms, into a cephalosporin skeleton containing six atoms. In organic chemistry you would need wizardry to do that. Enzymatically, that is much simpler, provided you have the correct enzyme at hand. The ring structure in the antibiotic molecule defines the way it works, the side chain defines the speed at which the molecule is absorbed. They really performed top science in Delft.’
All knowledge concentrated
In the early 1990s, three companies were reputed for their biocatalytic knowledge: Danish NOVO, and Dutch Gist-brocades and DSM (which later merged). DSM had a working relationship with NOVO, which produced not merely penicillins but also insulin. Then, NOVO judged the contamination risk of their insulin production with penicillins to be too high; insulin being much more important to them, they sold their penicillin knowledge to DSM. Just about then, Chemfern was formed, a joint venture of DSM and Gist-brocades, and DSM contributed this knowledge to the new business, as a kind of dowry. In other words: around 1995 all knowledge in the world about catalytic production of penicillins and their relatives, cephalosporins, was concentrated in Chemfern. Although this in itself was not enough for success, for that would also need production and marketing capabilities.’
‘Dutch government took up an interest, and we presented a plan to develop 