Serendipity outstrips design

摘要

Accelerated evolution of an artificial enzyme improved its activity several-thousand fold, owing to unexpectedly extreme remodelling of its active site. A team led by Donald Hilvert and Nenad Ban at the Swiss Federal Institute of Technology in Zurich optimized a computationally designed enzyme with several rounds of random mutagenesis and screening. The activity levels of the evolving enzyme eventually approached those of natural enzymes, but the protein no longer catalysed its reaction using the machinery the researchers had intended. An amino-acid residue installed to help rearrange bonds was abandoned for one that emerged at another location in the active site. Such swaps could be important in natural-enzyme evolution and design efforts, the authors say.