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Title: Purinyl-cobamide is a native prosthetic group of reductive dehalogenases

Abstract

Here, cobamides such as vitamin B 12 are structurally conserved, cobalt-containing tetrapyrrole biomolecules that have essential biochemical functions in all domains of life. In organohalide respiration, a vital biological process for the global cycling of natural and anthropogenic organohalogens, cobamides are the requisite prosthetic groups for carbon–halogen bond-cleaving reductive dehalogenases. This study reports the biosynthesis of a new cobamide with unsubstituted purine as the lower base and assigns unsubstituted purine a biological function by demonstrating that Coα-purinyl-cobamide (purinyl-Cba) is the native prosthetic group in catalytically active tetrachloroethene reductive dehalogenases of Desulfitobacterium hafniense. Cobamides featuring different lower bases are not functionally equivalent, and purinyl-Cba elicits different physiological responses in corrinoid-auxotrophic, organohalide-respiring bacteria. Given that cobamide-dependent enzymes catalyze key steps in essential metabolic pathways, the discovery of a novel cobamide structure and the realization that lower bases can effectively modulate enzyme activities generate opportunities to manipulate functionalities of microbiomes.

Authors:
 [1];  [2]; ORCiD logo [2];  [2]; ORCiD logo [3];  [3];  [3]; ORCiD logo [4];  [2];  [2];  [2]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4]
  1. Univ. of Tennessee, Knoxville, TN (United States); Chinese Academy of Sciences, Liaoning (People's Republic of China); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. Univ. of Toronto, Toronto, ON (Canada)
  4. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1471874
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 14; Journal Issue: 1; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Yan, Jun, Bi, Meng, Bourdon, Allen K., Farmer, Abigail T., Wang, Po -Hsiang, Molenda, Olivia, Quaile, Andrew T., Jiang, Nannan, Yang, Yi, Yin, Yongchao, Şimşir, Burcu, Campagna, Shawn R., Edwards, Elizabeth A., and Löffler, Frank E. Purinyl-cobamide is a native prosthetic group of reductive dehalogenases. United States: N. p., 2017. Web. doi:10.1038/nchembio.2512.
Yan, Jun, Bi, Meng, Bourdon, Allen K., Farmer, Abigail T., Wang, Po -Hsiang, Molenda, Olivia, Quaile, Andrew T., Jiang, Nannan, Yang, Yi, Yin, Yongchao, Şimşir, Burcu, Campagna, Shawn R., Edwards, Elizabeth A., & Löffler, Frank E. Purinyl-cobamide is a native prosthetic group of reductive dehalogenases. United States. doi:10.1038/nchembio.2512.
Yan, Jun, Bi, Meng, Bourdon, Allen K., Farmer, Abigail T., Wang, Po -Hsiang, Molenda, Olivia, Quaile, Andrew T., Jiang, Nannan, Yang, Yi, Yin, Yongchao, Şimşir, Burcu, Campagna, Shawn R., Edwards, Elizabeth A., and Löffler, Frank E. Mon . "Purinyl-cobamide is a native prosthetic group of reductive dehalogenases". United States. doi:10.1038/nchembio.2512. https://www.osti.gov/servlets/purl/1471874.
@article{osti_1471874,
title = {Purinyl-cobamide is a native prosthetic group of reductive dehalogenases},
author = {Yan, Jun and Bi, Meng and Bourdon, Allen K. and Farmer, Abigail T. and Wang, Po -Hsiang and Molenda, Olivia and Quaile, Andrew T. and Jiang, Nannan and Yang, Yi and Yin, Yongchao and Şimşir, Burcu and Campagna, Shawn R. and Edwards, Elizabeth A. and Löffler, Frank E.},
abstractNote = {Here, cobamides such as vitamin B12 are structurally conserved, cobalt-containing tetrapyrrole biomolecules that have essential biochemical functions in all domains of life. In organohalide respiration, a vital biological process for the global cycling of natural and anthropogenic organohalogens, cobamides are the requisite prosthetic groups for carbon–halogen bond-cleaving reductive dehalogenases. This study reports the biosynthesis of a new cobamide with unsubstituted purine as the lower base and assigns unsubstituted purine a biological function by demonstrating that Coα-purinyl-cobamide (purinyl-Cba) is the native prosthetic group in catalytically active tetrachloroethene reductive dehalogenases of Desulfitobacterium hafniense. Cobamides featuring different lower bases are not functionally equivalent, and purinyl-Cba elicits different physiological responses in corrinoid-auxotrophic, organohalide-respiring bacteria. Given that cobamide-dependent enzymes catalyze key steps in essential metabolic pathways, the discovery of a novel cobamide structure and the realization that lower bases can effectively modulate enzyme activities generate opportunities to manipulate functionalities of microbiomes.},
doi = {10.1038/nchembio.2512},
journal = {Nature Chemical Biology},
issn = {1552-4450},
number = 1,
volume = 14,
place = {United States},
year = {2017},
month = {11}
}

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Works referenced in this record:

The Genetic Basis for Bacterial Mercury Methylation
journal, February 2013


One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products
journal, May 2000

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