In this publication, lead by Prof. Rebecca Buller from the ZHAW Wädenswil, Switzerland – we report that by removing destabilizing mutations from sequence space through computation and advanced molecular biology techniques, we could generate a Kemp eliminase that accelerates the proton abstraction step >10^8-fold in only 5 rounds of evolution. Recombining the resulting variant with a previously evolved Kemp eliminase HG3.17, which exhibits similar activity but differs by 29 substitutions, allowed us to chart the topography of the designer enzyme’s fitness landscape ? highlighting the existence of more than one proverbial ‘needle in the haystack’ !, see here.
Article published in Nature Chemical Biology
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