Studies on the enzymatic synthesis of optically pure tertiary alcohols: Biocatalysis and Protein Design

This books deals with a catalytic platform for the enzymatic synthesis of tertiary alcohols. A certain class of hydrolases bearing the GGG(A)X-motif are efficient and highly selective catalysts for this difficult reaction. The number of available biocatalysts could be extended by making use of a structure-guided screening in metagenome-derived enzyme libraries. Two highly selective enzymes were identified. One model enzyme, esterase BS2, was optimized and the hydrolysis of tertiary esters was studied in detail. In a protein design study, novel enzyme variants were generated by semi-rational protein design methods, which led to the identification of mutants with strongly increased or even inverse enantioselectivity. The application of the platform to the kinetic resolution of a building block of pharmaceutical interest is described.