Abstract
Controlled halogenation of chemically versatile substrates is difficult to achieve. Here we describe a unique flavin-dependent halogenase, PltM, which is capable of utilizing a wide range of halides for installation on a diverse array of phenolic compounds, including FDA-approved drugs and natural products, such as terbutaline, fenoterol, resveratrol, and catechin. Crystal structures of PltM in complex with phloroglucinol and FAD in different states yield insight into substrate recognition and the FAD recycling mechanism of this halogenase.
| Original language | English |
|---|---|
| Article number | 1255 |
| Journal | Nature Communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2019 |
Bibliographical note
Publisher Copyright:© 2019, The Author(s).
Funding
This work was supported by a NSF CAREER Award MCB-1149427 (to S.G.-T.), a grant as part of the National Center for Advancing Translational Sciences (UL1TR000117) (to S.G.-T. and O.V.T.), and by startup funds from the College of Pharmacy at the University of Kentucky (to S.G.-T. and O.V.T.). S.M. is a recipient of a 2018 long-term visit fellowship from the Yamada Science Foundation, Japan. The authors thank Dr. James J. La Clair and Prof. Michael D. Burkart from UCSD for valuable discussion and suggestions on optimization of PltM reaction conditions for halogenation. The authors are grateful to the staff of sector SER-CAT of Advanced Photon Source of the Argonne National Laboratory for support during the remote data collection.
| Funders | Funder number |
|---|---|
| Yamada Science Foundation | |
| University of Kentucky | |
| National Science Foundation Arctic Social Science Program | MCB-1149427, 1149427 |
| National Center for Advancing Translational Sciences (NCATS) | UL1TR000117 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General
- General Physics and Astronomy
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