Molecular Interaction Engineering (Helmholtz Research Network) Subproject SynCasc
Dr. Jens Rudat
Molecular Interaction Engineering (MIE)
Subproject "Synthetic reaction cascades" (SynCasc)
Project description: http://www.forschung-mie.de
Their selectivity and mild reaction conditions make biocatalysts sought-after catalysts of chiral fine chemicals, especially for the pharmaceutical industry. By coupling naturally occurring enzymes from different microorganisms with tailor-made synthetic biocatalysts, compounds not found in nature can also be biobased under technical ambient conditions. With enzyme cascades, new synthesis routes can be opened up on this basis and classical chemical syntheses can be replaced on a sustainable basis:
(Please click on the image for a larger representation)
Schematic representation of the structure of modular enzyme cascades. Individual reactions of immobilized biocatalysts are to be combined. In parallel, "enzyme engineering" is to enable a higher substrate selection and thus open up a greater variety of products.
Within the framework of the projects SC-1 and SC-2, different enzymatic processes for the synthesis of non-canonical amino acids as well as chiral alcohols with pharmacological relevance are being established at KIT and FZJ. In this context, the focus of the Syldatk/Rudat group (SC-1) is on the production of aromatic chiral α- and β-amino acids (e.g. β-phenylalanine derivatives), which have so far only been accessible via chemoenzymatic racemate cleavage with a maximum yield of 50%. For this purpose, amidases are used for the stereoselective cleavage of hydantoin derivatives, the chemical or enzymatic racemization of which allows 100% yield. Alternatively, β-amino acids are to be prepared by lipase-transaminase coupling starting from 3-oxo-3-arylpropionic acid esters, in which a 100% reaction yield is also possible.
The modular enzyme cascades will initially be established as hybrid cell-free systems. The long-term goal is to provide a reaction compartment consisting of two to three coupled tailored enzymes or chemo- and biocatalytic functional components that can convert different molecules of a compound class to the desired product via controlled multistep synthesis by means of increased substrate diversity.