Industrial Applications of Whole-Cell Biocatalysis - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
27%
Attracting a skilled workforce
27%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
32%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here