Understanding Flavin-Dependent Halogenase Reactivity Via Substrate Activity Profiling

Overview

Journal ACS Catal

Publisher American Chemical Society

Date 2017 Oct 10

PMID 28989809

Citations 38

Authors

Mary C Andorfer

Jonathan E Grob

Christine E Hajdin

Julia R Chael

Piro Siuti

Jeremiah Lilly

Kian L Tan

Jared C Lewis

Affiliations

Soon will be listed here.

Abstract

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 impact FDH activity and selectivity. The enzymes studied could halogenate a far greater range of substrates than 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.

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