Pharmaaminosäuren, LOLA, CREAVIS

Fermentation


Pharmaceutical amino acids from the bioreactor


Amino acids and their derivatives are indispensable raw materials for important active pharmaceutical ingredients; they ensure the correct balance of nutrients in parenteral nutrition and also play an important role as nutritional supplements. That Evonik is one of the world’s leading suppliers of amino acids for various markets and applications is also undoubtedly due to the work of researchers at Creavis.

In contrast to the amino acids used in animal nutrition, the pharmaceutical amino acids distributed by Evonik under the REXIM® brand name were originally obtained from animal raw materials. For this purpose keratin or gelatine, for example, were processed to give protein hydrolysates. It was possible to obtain up to 15 different amino acids from a single batch. 

At the turn of the century, however, amino acid production from animal raw materials became less acceptable, mainly because of concerns about Transmissible Spongiform Encephalopathies like BSE—although the procedures are still considered scientifically safe. In 2003 the decision was finally made at Degussa, a predecessor company of Evonik, to switch completely to biotechnological processes for amino acid production.

This decision did not come as a complete surprise. Back in the early 1980s, the company had already begun to investigate the potential of biotechnology. The first enzyme membrane reactor for production of L-amino acids went into operation in 1981; this was the first time that biotransformation reactions with dissolved enzymes had been carried out continuously on a technical scale.

Eleven of the former 23 business units were involved in the Biotechnology Project House established at Creavis in 2001. For three years, researchers worked to develop new enzyme systems in this facility, which was to operate for a specified period of time. Finally, in the ProFerm Project House from 2003 onwards, the technological foundations were laid for a complete changeover of pharmaceutical amino acid production to biotechnological processes. In 2006 this achievement received an Evonik Innovation Award.  

The first amino acid that Evonik produced using the new fermentation method was L proline, which was manufactured by its Slovakian subsidiary Fermas. Processes for further amino acids were added in rapid succession. Today the product range of the Health Care Business Line includes about a dozen pharmaceutical amino acids that are manufactured using biotechnological methods. 

One example is L-ornithine, an amino acid that plays an important role in nitrogen metabolism in the human body. Within the activities of the Creavis’s Biotechnology Science-to-Business Center, a fermentation process was developed in 2007 that enables the amino acid to be produced directly from sugar. By specifically optimizing the metabolic pathway of the bacteria, the scientists managed to more than double the performance of the bacteria and, at the same time, eliminate critical by-products. Since the end of 2009, large-scale production of L-ornithine and its derivatives has been carried out at Evonik’s Ham site in France, in collaboration with Fermas. In the meantime the Health Care Business Line has further optimized the strain and the process, with a significant further increase in the productivity and yield of the process and a marked decline in the formation of by-products.

Since then, Creavis’s researchers have been working continuously to expand the possibilities for using biotechnology at Evonik. Currently, for example, they are working on the use of obligate anaerobic bacteria to produce specialty chemicals. But that’s another story.

Rheticus Project