Combining efforts in enzyme and process engineering to improve access to multifunctional chiral intermediates

Acronym: ProAChIm

Results of ProAChIm
(click here)

Project coordinator
- Prof. Martin Bertau - Freiberg University of Mining and Technology -
Project leaders
- Dr. Antje Eichler - Junior Research Group Industrial
  Biotechnology - Germany
- Prof. Wladimir Reschetilowski - Technische Universität Dresden -
- Dr. Thomas Greiner-Stöffele - c-LEcta GmbH - Germany
- Prof. Adrzej Kolinski - University of Warsaw - Poland
- Prof. Volker Hessel - Eindhoven University of Technology - The
- Wessel Hengeveld (industrial observer) - Flowid B.V. - The
- Dr. Wille Gregor (industrial observer) - Sigma-Aldrich Production
  GmbH - Germany

Most of the top-selling drugs today, like the cholesterol lowering “Atorvastatine”, are chiral, i.e. they contain one or more stereogenic centres. To produce these chiral drugs, small chiral building blocks are required as a starting material. Hence provision and thus synthesis of the latter in an efficient, economical and preferentially ecological way is of increasing importance in order to ensure the supply of state-of-the-art drugs at a reasonable price.
This project addresses the latter issue by focusing on the synthesis of a certain group of chiral building blocks named -amino-alcohols. These substances are known to be valuable in the synthesis of various -sympathomimetics, anti-parkinsons-disease-drugs and even antibiotics.
Enantiomerically enriched -amino-alcohols are theoretically accessible in an ecological and economical way by using enzymes. However, most of the amino-alcohol producing enzymes known today only accept a limited number of substrates and show unsatisfying stereoselectivity. Thus the first aim of this project is to identify new enzymes which are subsequently optimised and adjusted to the process needs using mutagenesis guided by in silico enzyme modelling.
A further challenge which hampers application of enzymes in biocatalytic synthesis of chiral amino-alcohols lies in the reversibility of the reaction. As a consequence a high yield is only achievable if measures are taken to shift the equilibrium of the reaction towards the side of the products. The second aim of the project will attend to that by investigating consecutive reactions coupled to the primary one in order to make the overall reaction practically irreversible. This will also be facilitated by innovations in process chemistry. Thereby the project is aimed at running the process in micro-structured reactors allowing operation in novel process windows, in which the reaction is intensified and run continuously.
With the established project consortium bringing together experts from various fields such as biochemistry, bioinformatics, industrial chemistry and micro-reactor engineering, the project is expected to yield new enzymes and a new process which together will improve access to enantiopure -amino-alcohols. As enzymes and the process are expected to be commercially available, industry is enabled to benefit from the results of the project.