Tungsten enzymes play a role in detoxifying food and antimicrobial aldehydes in the human gut microbiome

Abstract

Significance The diverse microorganisms contained within the human gut are known to have significant effects on human health. Herein, we show that genes encoding members of the tungsten oxidoreductase (WOR) family of enzymes and a tungstate-specific transporter are prevalent in the human gut microbiome and metagenome. We demonstrate that two model gut microbes assimilate tungsten into multiple WOR enzymes and that some of these enzymes catalyze the conversion of gut aldehydes to the corresponding acid, likely as a detoxification strategy to remove these reactive compounds.

A tungsten enzyme using hydrogen as an electron donor to reduce carboxylic acids and NAD+

“…They catalyze the oxidation of various aldehydes to the respective acids and are grouped into several branches according to their sequence conservation and their substrate preference: e.g. oxidoreductases for formaldehyde (FOR) 8 , glyceraldehyde phosphate (GAPOR 9 and GOR 10 ), or wide-range spectra of different aldehydes (AOR sensu stricto [11][12][13][14][15][16] or WOR5 17 ). They are unique in biochemistry also for their ability to catalyse the thermodynamically di cult reduction of nonactivated carboxylic acids to aldehydes, which usually needs prior activation to acyl phosphates or acyl thioesters 12,15,18,19 .…”

“…1A), acid reduction requires such low-potential electron donors and still proceeds only at rates of less than 5% of those observed for aldehyde oxidation 18,19 . AORs were previously thought to occur predominantly in thermophilic anaerobic microorganisms, such as the archaeal genera Pyrococcus or Thermococcus or the bacterial species M. thermoacetica 20,21 , but recent ndings show that these enzymes are much more widespread and also occur in many mesophilic species of strictly or facultative anaerobic Archaea and Bacteria 1,15,16,22,23 .…”

A tungsten enzyme using hydrogen as an electron donor to reduce carboxylic acids and NAD+

“…Moreover, it appears that the observed acid reduction process does not actually qualify as an endergonic reaction, because the enzyme just reaches aldehyde concentrations close to the thermodynamic equilibrium. Therefore, AOR Aa apparently does not belong to the growing list of anaerobic enzymes exhibiting electron bifurcation, despite a recent report on an AOR Aa from an anaerobic gut bacterium, which claims an electron bifurcation process, but lacks su cient control experiments 16 .…”

“…They catalyze the oxidation of various aldehydes to the respective acids and are grouped into several branches according to their sequence conservation and their substrate preference: e.g. oxidoreductases for formaldehyde (FOR) 8 , glyceraldehyde phosphate (GAPOR 9 and GOR 10 ), or wide-range spectra of different aldehydes (AOR sensu stricto [11][12][13][14][15][16] or WOR5 17 ). They are unique in biochemistry also for their ability to catalyse the thermodynamically di cult reduction of nonactivated carboxylic acids to aldehydes, which usually needs prior activation to acyl phosphates or acyl thioesters 12,15,18,19 .…”

“…1A), acid reduction requires such low-potential electron donors and still proceeds only at rates of less than 5% of those observed for aldehyde oxidation 18,19 . AORs were previously thought to occur predominantly in thermophilic anaerobic microorganisms, such as the archaeal genera Pyrococcus or Thermococcus or the bacterial species M. thermoacetica 20,21 , but recent ndings show that these enzymes are much more widespread and also occur in many mesophilic species of strictly or facultative anaerobic Archaea and Bacteria 1,15,16,22,23 . One of these AORs has recently been characterised from the betaprotebacterium Aromatoleum aromaticum (AOR Aa ).…”