Post doc opportunity – Tungsten-Containing Enzymes in Human Gut Microbes (funded by NIH) – University of Georgia

The NIH Human Microbiome Project (HMP) has revolutionized our perspective on humanmicrobe

interactions and provided a tremendous impetus for research in order to obtain a much

deeper understanding of how microbes impact human health. The gut microorganisms of the

HMP Reference Genomes and the Human Gastrointestinal Bacteria Culture Collection contain

961 species representing 142 genera. Yet, relatively little is known about these specific gut

microbes. Herein we will test the hypothesis that tungsten (W), a metal almost never considered

in biological systems, is essential for the health of the human gut microbiome. Our bioinformatics

analyses reveal that a large number of these gut microbes contain genes encoding diverse

members of the W-containing oxidoreductase (WOR) family of enzymes. Only a very few WOR

enzymes have been previously characterized, mainly from exotic thermophilic microbes. The

overall goal of the proposed research is to show that other members of the WOR family have

essential functions in the gut microbiome. In preliminary studies, we have shown that some gut

microbes take up trace amounts of W and their W-containing WORs remove reactive and

potentially toxic aldehydes found in the gut, which are generated from cooked foods and

microbiome metabolism. Other W-containing WORs proposed to catalyze other as yet unknown

reactions. In the proposed research we will purify ten novel phylogenetically distinct WORs by

W-monitored (using ICP-MS) anaerobic chromatography. Their catalytic activities and

physiological substrates will be determined by an enzyme-induced metabolomics approach (using

LC-MS). In addition, we propose that some of these WORs are electron bifurcating enzymes that

simultaneously couple exergonic and endergonic reactions, a recently discovered mechanism of

energy conservation in biological systems. Kinetic, spectroscopic and structural (using cryoEM)

analyses of this subset of W-enzymes will be used to investigate the nature of the bifurcation

reactions and what their functions are in the gut microbiome. Using genome-based metabolic

reconstructions, the physiological functions of the various WORs will be ascertained and we will

determine the effects of W on the metabolism of the gut microbes, including on their resistance to

gut- and cooking-related aldehydes.

It is now clear that, in addition to facilitating digestion, the gut microbiome plays roles in a

surprisingly extensive range of human conditions, including in Parkinson’s, schizophrenia,

osteoarthritis and in cardiovascular, liver and immune-deficiency diseases. The results of the this

research will provide a completely new perspective on the primary metabolisms of the key

microbes in our gastrointestinal tract and the proposed essential role of tungsten, a metal that was

thought to be seldom used in biological systems.

Interested?  Email Mike Adams (, University of Georgia