view article
Figure 1
A prominent example of semi-rational directed evolution of an (R)-selective amine transaminase for sitagliptin manufacture (Savile et al., 2010BB80). Shown here is the structure of the final variant after 11 rounds of evolution (PDB entry 5fr9; Cuetos et al., 2016BB19). Achieving this industrially applicable enzyme required 27 amino-acid substitutions, the positions of which are highlighted here in blue in both chains of the structure. This figure illustrates how diversely distributed across an enzyme functionally important residues can be, and therefore why it can be so hard to predict appropriate amino-acid substitutions using only rational design approaches. Chain A is coloured light grey and chain B green, and the covalent cofactor–inhibitor complex of both subunits is shown in dark grey using a ball-and-stick representation for better clarity. This and all figures showing crystal structures were created using the PyMOL Molecular Graphics System (Version 1.8, Schrödinger LLC).

IUCrJ
Volume 4| Part 1| January 2017| Pages 50-64
ISSN: 2052-2525
https://doi.org/10.1107/S2052252516018017