Swiss Science Concentrates

摘要

Most metalloenzymes exhibit extraordinarily high catalytic activity and substrate specificity as the result of millions of years of evolution. In their recent publication, Hilvert and coworkers recapitulated a possible mechanism of metalloprotein biogenesis from short peptides. Starting from the homodimeric, zinc-binding MID1-peptide, several rounds of targeted and random mutagenesis were combined with computational redesign to simultaneously re-optimize structure and function. The active site of the generated globular enzyme MID1sc10 esterase strongly resembled that of native zinc enzymes, while exhibiting a high catalytic activity (k_cat)/K_M ~ 10~6 M~(-1) s~(-1)) and high enantioselectivity. The novel and innovative approach therefore not only offers insights into the putative biogenesis of these natural catalysts, but also contributes greatly to the scientific fields of enzyme design and engineering.