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

Autor: Carlson HK; Energy & Biosciences Institute, University of California, Berkeley, Berkeley, CA, 94720, USA. hkcarlson@lbl.gov.; Environmental Genomics and Systems Biology, Lawrence Berkeley National Lab, 1 Cyclotron Road, Berkeley, CA, 94704, USA. hkcarlson@lbl.gov., Youngblut MD; Energy & Biosciences Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.; Twist Bioscience, 681 Gateway Blvd, South San Francisco, CA, 94080, USA., Redford SA; Energy & Biosciences Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.; Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL, USA., Williamson AJ; Energy & Biosciences Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.; CENBG, Université de Bordeaux, CNRS-IN2P3/, 19 Chemin du Solarium, CS10120, 33175, Gradignan, France., Coates JD; Energy & Biosciences Institute, University of California, Berkeley, Berkeley, CA, 94720, USA.; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, 94720, USA.
Jazyk: angličtina
Zdroj: ISME communications [ISME Commun] 2021 Nov 13; Vol. 1 (1), pp. 67. Date of Electronic Publication: 2021 Nov 13.
DOI: 10.1038/s43705-021-00069-1
Abstrakt: 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 (k cat , K M ) for alternative substrates (molybdate, selenate, arsenate, monofluorophosphate, and chromate) and inhibition constants (K I ) 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 (IC 50 ) based on Sat kinetics with measured IC 50 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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