Unusual Substrate and Halide Versatility of Phenolic Halogenase PltM

Authors

Shogo Mori, University of KentuckyFollow
Allan H. Pang, University of Kentucky
Nishad Thamban Chandrika, University of KentuckyFollow
Sylvie Garneau-Tsodikova, University of KentuckyFollow
Oleg V. Tsodikov, University of KentuckyFollow

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.

Document Type

Article

Publication Date

3-19-2019

Notes/Citation Information

Published in Nature Communications, v. 10, article no. 1255, p. 1-11.

© The Author(s) 2019

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

A correction to this article is available as the additional file listed below and online at https://doi.org/10.1038/s41467-019-09731-8.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41467-019-09215-9

Funding Information

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.

Related Content

The crystal structure coordinates and structure factor amplitudes for all crystal structures were deposited in the Protein Data Bank under accession codes 6BZN, 6BZI, 6BZA, 6BZQ, 6BZT and 6BZZ, as described in Supplementary Tables 4 and 5. NMR spectra, LC-MS, and other chromatographic data are included in the raw format in Supplementary Information. Other data are available from the corresponding authors upon reasonable request.

Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467- 019-09215-9.

Repository Citation

Mori, Shogo; Pang, Allan H.; Thamban Chandrika, Nishad; Garneau-Tsodikova, Sylvie; and Tsodikov, Oleg V., "Unusual Substrate and Halide Versatility of Phenolic Halogenase PltM" (2019). Pharmaceutical Sciences Faculty Publications. 137.
https://uknowledge.uky.edu/ps_facpub/137