129511-06-4Relevant academic research and scientific papers
Understanding Flavin-Dependent Halogenase Reactivity via Substrate Activity Profiling
Andorfer, Mary C.,Grob, Jonathan E.,Hajdin, Christine E.,Chael, Julia R.,Siuti, Piro,Lilly, Jeremiah,Tan, Kian L.,Lewis, Jared C.
, p. 1897 - 1904 (2017/08/17)
The activity of four native FDHs and four engineered FDH variants on 93 low-molecular-weight arenes was used to generate FDH substrate activity profiles. These profiles provided insights into how substrate class, functional group substitution, electronic activation, and binding affect FDH activity and selectivity. The enzymes studied could halogenate a far greater range of substrates than have been previously recognized, but significant differences in their substrate specificity and selectivity were observed. Trends between the electronic activation of each site on a substrate and halogenation conversion at that site were established, and these data, combined with docking simulations, suggest that substrate binding can override electronic activation even on compounds differing appreciably from native substrates. These findings provide a useful framework for understanding and exploiting FDH reactivity for organic synthesis.
