Industrial Applications of Whole-Cell Biocatalysis - Pharmaceutical Technology

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Industrial Applications of Whole-Cell Biocatalysis
Recombinant microbial whole-cell biocatalysis is a valuable approach for producing enantiomerically pure interemediates. The authors examine several groups of enzymes using this approach: dehydrogenases, hydantoinases, and acylases.


Pharmaceutical Technology


Conclusion

The examples show the successful development of biocatalytic technologies for producing optically pure amino acids and other fine chemicals. Evonik has developed two different dynamic kinetic resolution processes for producing natural and nonnatural L-amino acids that allow a broad range of relevant substrates. The first process is based on the resolution of 5'-monosubstituted hydantoins, and the second process is based on the resolution of N-acetyl amino acids using an acylase in combination with a racemase.

These technologies have been recently expanded by a process using oxido-reductases and a cofactor regeneration system for producing amino acids and chiral molecules starting from prochiral ketones. Whether the oxidoreductase platform, the L-hydantoinase process or the combination of an L-acylase with an N-acetyl-amino acid racemase is superior, is strongly dependent on the specific product in demand and influenced by the biocatalyst properties as well as the cheapest access to the substrate.

All approaches together provide a high degree of flexibility producing a number of different L-amino acids, which is especially important for fast-changing product demands typical of the fine-chemicals and pharmaceutical industries.

Wolfgang Wienand is director of the industry segment photovoltaics of the inorganic materials business unit and Kai Doderer and Steffen Osswald* are project managers at the Service Center Biocatalysis in the health and nutrition business unit at Evonik Degussa GmbH, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany, tel. +49 6181.59.6748, fax +49.6181.59.76748,
Ulrich Becker is a pilot-plant manager at Evonik's Service Center Biocatalysis. Stefan Verseck is head of biotechnology at Cognis GmbH.

*To whom all correspondence should be addressed.

References

1. K. Nakamura and T. Matsuda, "Enzyme Catalysis" in Organic Synthesis, K. Drauz and H. Waldmann Eds., (Wiley-VCH, Weinheim, Vol. 3, 2nd ed., 2002), pp. 991–1047.

2. W. Hummel, "New Alcohol Dehydrogenases for the Synthesis of Chiral Compounds," Adv. Biochem. Eng. Biotechnol. 58, 146–184 (1997).

3. K. Faber, "Biotransformations" in Organic Chemistry (Springer-Verlag, Berlin, 5th ed., 2004), pp. 192–197.

4. H. Gröger et al., "Enantioselective Reduction of Ketones with Designer Cells at High Substrate Concentrations: Highly Efficient Access to Functionalized Optically Active Alcohols," Angew. Chem. Int. Ed. 45 (34) 5677–5681 (2006).

5. M.R. Kula and C. Wandrey, "Continuous Enzymatic Transformation in an Enzyme-Membrane Reactor with Simultaneous NADH Regeneration," in Methods in Enzymology, K. Mosback, Ed. (Vol. 136, 1987), pp. 9-21.

6. A. Bommarius, M. Schwarm, and K.H. Drauz, "Biocatalysis to Amino Acid-based Chiral Pharmaceuticals—Examples and Perspectives," J. Mol. Catal. B Enzy. 5 (1–4), 1–11 (1998).


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