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Title: Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration

Abstract

Abstract Sulfate analog oxyanions that function as selective metabolic inhibitors of dissimilatory sulfate reducing microorganisms (SRM) are widely used in ecological studies and industrial applications. As such, it is important to understand the mode of action and mechanisms of tolerance or adaptation to these compounds. Different oxyanions vary widely in their inhibitory potency and mechanism of inhibition, but current evidence suggests that the sulfate adenylyl transferase/ATP sulfurylase (Sat) enzyme is an important target. We heterologously expressed and purified the Sat from the model SRM, Desulfovibrio alaskensis G20. With this enzyme we determined the turnover kinetics (kcat, KM) for alternative substrates (molybdate, selenate, arsenate, monofluorophosphate, and chromate) and inhibition constants (KI) for competitive inhibitors (perchlorate, chlorate, and nitrate). These measurements enable the first quantitative comparisons of these compounds as substrates or inhibitors of a purified Sat from a respiratory sulfate reducer. We compare predicted half-maximal inhibitory concentrations (IC50) based on Sat kinetics with measured IC50 values against D. alaskensis G20 growth and discuss our results in light of known mechanisms of sensitivity or resistance to oxyanions. This analysis helps with the interpretation of recent adaptive laboratory evolution studies and illustrates the value of interpreting gene–microbe–environment interactions through the lens of enzymemore » kinetics.« less

Authors:
ORCiD logo; ; ORCiD logo; ; ORCiD logo
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1830237
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
ISME Communications
Additional Journal Information:
Journal Name: ISME Communications Journal Volume: 1 Journal Issue: 1; Journal ID: ISSN 2730-6151
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English

Citation Formats

Carlson, Hans K., Youngblut, Matthew D., Redford, Steven A., Williamson, Adam J., and Coates, John D. Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration. United States: N. p., 2021. Web. doi:10.1038/s43705-021-00069-1.
Carlson, Hans K., Youngblut, Matthew D., Redford, Steven A., Williamson, Adam J., & Coates, John D. Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration. United States. https://doi.org/10.1038/s43705-021-00069-1
Carlson, Hans K., Youngblut, Matthew D., Redford, Steven A., Williamson, Adam J., and Coates, John D. Sat . "Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration". United States. https://doi.org/10.1038/s43705-021-00069-1.
@article{osti_1830237,
title = {Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration},
author = {Carlson, Hans K. and Youngblut, Matthew D. and Redford, Steven A. and Williamson, Adam J. and Coates, John D.},
abstractNote = {Abstract Sulfate analog oxyanions that function as selective metabolic inhibitors of dissimilatory sulfate reducing microorganisms (SRM) are widely used in ecological studies and industrial applications. As such, it is important to understand the mode of action and mechanisms of tolerance or adaptation to these compounds. Different oxyanions vary widely in their inhibitory potency and mechanism of inhibition, but current evidence suggests that the sulfate adenylyl transferase/ATP sulfurylase (Sat) enzyme is an important target. We heterologously expressed and purified the Sat from the model SRM, Desulfovibrio alaskensis G20. With this enzyme we determined the turnover kinetics (kcat, KM) for alternative substrates (molybdate, selenate, arsenate, monofluorophosphate, and chromate) and inhibition constants (KI) for competitive inhibitors (perchlorate, chlorate, and nitrate). These measurements enable the first quantitative comparisons of these compounds as substrates or inhibitors of a purified Sat from a respiratory sulfate reducer. We compare predicted half-maximal inhibitory concentrations (IC50) based on Sat kinetics with measured IC50 values against D. alaskensis G20 growth and discuss our results in light of known mechanisms of sensitivity or resistance to oxyanions. This analysis helps with the interpretation of recent adaptive laboratory evolution studies and illustrates the value of interpreting gene–microbe–environment interactions through the lens of enzyme kinetics.},
doi = {10.1038/s43705-021-00069-1},
journal = {ISME Communications},
number = 1,
volume = 1,
place = {United States},
year = {Sat Nov 13 00:00:00 EST 2021},
month = {Sat Nov 13 00:00:00 EST 2021}
}

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