Structural highlights
Publication Abstract from PubMed
Reduction of double bonds of alpha,beta-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.
Structural insights into the ene-reductase synthesis of profens.,Waller J, Toogood HS, Karuppiah V, Rattray NJW, Mansell DJ, Leys D, Gardiner JM, Fryszkowska A, Ahmed ST, Bandichhor R, Reddy GP, Scrutton NS Org Biomol Chem. 2017 May 9. doi: 10.1039/c7ob00163k. PMID:28485453[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Waller J, Toogood HS, Karuppiah V, Rattray NJW, Mansell DJ, Leys D, Gardiner JM, Fryszkowska A, Ahmed ST, Bandichhor R, Reddy GP, Scrutton NS. Structural insights into the ene-reductase synthesis of profens. Org Biomol Chem. 2017 May 9. doi: 10.1039/c7ob00163k. PMID:28485453 doi:http://dx.doi.org/10.1039/c7ob00163k
