Cycles of disruption and repair underlie the evolution of new enzyme function — ASN Events
  1. Schedule
  2. Session 10: Poster Session C
  3. Cycles of disruption and repair underlie the evolution of new enzyme function

Cycles of disruption and repair underlie the evolution of new enzyme function (#363)

Eleanor Campbell 1 , Paul D Carr 1 , Miriam Kaltenbach 2 , Nobuhiko Tokuriki 2 , Colin J Jackson 1
  1. Australian National University, Canberra, ACT, Australia
  2. University of British Columbia, Vancouver, Canada

This research describes the structural characterisation of a number of bacterial phosphotriesterase (PTE) variants along a molecular evolution trajectory. The molecular evolution experiment saw the activity of PTE altered from a phosphotriesterase to an arylesterase, capable of catalysing the hydrolysis of the arylester bond in the substrate 2-naphthyl hexanoate (2NH)1 .While the presence and purposes of conformational sub-structures have been established for wild type PTE, the role of conformational variety has not been determined in the context of a molecular evolution pathway.2

Through the construction and analysis of crystal structures of variants from this evolutionary trajectory, several regions crucial to altering PTE activity were identified. Investigation of the structures revealed stepwise evolution of key regions, showing the conformational flexibility of each region peaking at different points throughout the trajectory, before being stabilised to facilitate the new arylesterase activity. The correlation between the bifunctionality of some PTE variants and their high conformational variability suggests that conformational sub-structures form the basis of enzyme promiscuity.



  1. Tokuriki, N. et al. Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme. Nat. Commun. 3, 1 - 9 (2012).
  2. Jackson, C. J. et al. Conformational sampling, catalysis, and evolution of the bacterial phosphotriesterase. Proc. Natl. Acad. Sci. USA 106, 21631 - 21636 (2009).