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A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments
 

Summary: A diverse family of thermostable cytochrome P450s
created by recombination of stabilizing fragments
Yougen Li1, D Allan Drummond2,3, Andrew M Sawayama1, Christopher D Snow1, Jesse D Bloom1 &
Frances H Arnold1
Thermostable enzymes combine catalytic specificity with
the toughness required to withstand industrial reaction
conditions1,2. Stabilized enzymes also provide robust
starting points for evolutionary improvement of other
protein properties3. We recently created a library4 of at least
2,300 new active chimeras of the biotechnologically
important59 cytochrome P450 enzymes. Here we show
that a chimera's thermostability can be predicted from the
additive contributions of its sequence fragments. Based on
these predictions, we constructed a family of 44 novel
thermostable P450s with half-lives of inactivation
at 57 1C up to 108 times that of the most stable parent.
Although they differ by as many as 99 amino acids
from any known P450, the stable sequences are
catalytically active. Among the novel functions they exhibit
is the ability to produce drug metabolites. This chimeric

  

Source: Arnold, Frances H. - Division of Chemistry and Chemical Engineering, California Institute of Technology

 

Collections: Chemistry; Biology and Medicine