Biocatalytic Processes in Nonaqueous Environments: Benefits, Limitations and Prospects

Professor Alex Klibanov, MIT, USA

The keynote presentation given by Professor Klibanov covered major developments in applied biocatalysis from 1980 to the present and some predictions of the future. Methods for enhancing the enantioselectivity of a given enzyme in a given reaction such as varying the solvent, modifying the history of the enzyme sample or temporarily enlarging the chiral substrate were described.

So for example the activity and the stereoselectivity of the acylation of the pro-R or the pro-S hydroxyl of 2-(3,5-dimethoxybenzyl)propane-1,3-diol using chymotrypsin can be varied simply by changing the solvent. These differences arise because of the differential free energy of solvation in the transition states. The solvent dependence of the prochiral selectivity also depends on the method of preparation of the chymotrypsin (results with cross linked crystalline material, lyophilised or acetone precipitated chymotrypsin were presented).

The enantioselectivity of the kinetic transesterification or selective acylation of racemic amino acid or derivatives can also be modified by forming a salt with a bulky counter ion. The selectivity of the acylation of 1-(hydroxymethyl)phenylacetic acid with vinyl acetate with P. cepacia lipase can be increased by a factor of 7 by using an adamantamine or quinuclidine salt as the substrate. In the final section of the talk, some examples of unnatural reactions, such as asymmetric sulfoxidation were presented including an example where changing the oxidant from hydrogen peroxide to tert-butyl hydroperoxide led to an inversion of the stereoselectivity.