Predicted AS3MT Proteins Methylate Arsenic and Support Two Major Phylogenetic AS3MT Groups

Abstract

Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, methylate inorganic arsenic to mono-, di-, and trimethylated arsenic metabolites, which the organism can excrete. In humans and other eukaryotic organisms, the arsenite methyltransferase (AS3MT) protein methylates arsenite. AS3MT sequences from eukaryotic organisms group phylogenetically with predicted eubacterial AS3MT sequences, which has led to the suggestion that AS3MT was acquired from eubacteria by multiple events of horizontal gene transfer. In this study, we evaluated whether 55 (out of which 47 were predicted based on protein sequence similarity) sequences encoding putative AS3MT orthologues in 47 species from different kingdoms can indeed methylate arsenic. Fifty-three of the proteins showed arsenic methylating capacity. For example, the predicted AS3MT of the human gut bacterium Faecalibacterium prausnitzii methylated arsenic efficiently. We performed a kinetic analysis of 14 AS3MT proteins representing two phylogenetically distinct clades (Group 1 and 2) that each contain both eubacterial and eukaryotic sequences. We found that animal and bacterial AS3MTs in Group 1 rarely produce trimethylated arsenic, whereas Hydra vulgaris and the bacterium Rhodopseudomonas palustris in Group 2 produce trimethylated arsenic metabolites. These findings suggest that animals during evolution have acquired different arsenic methylating phenotypes from different bacteria. Further, it shows that humans carry two bacterial systems for arsenic methylation: one bacterium-derived AS3MT from Group 1 incorporated in the human genome and one from Group 2 in F. prausnitzii present in the gut microbiome.

Arsenite Methyltransferase Diversity and Optimization of Methylation Efficiency

“…ArsMs with three domains have a relatively low arsenic methylation activity, converting 15–42% of As­(III) into methylated species (Table ). One exception is the thermophilic CmArsM, which produces 66% methylated species and with DMAs­(V) as the primary product at 70 °C, perhaps because rates of catalysis are generally higher at elevated temperatures. (Again, the actual products are likely trivalent but are oxidized in air or during analysis.)…”

“…ArsMs from different organisms show different methylation efficiencies and can be classified into two groups . Three-domain ArsMs in Group 1 exhibit low arsenic methylation activity and produce little volatile TMAs­(III).…”

Biomarkers of seafood intake during pregnancy – Pollutants versus fatty acids and micronutrients

“…Urinary arsenobetaine, trimethylarsine oxide, and arsenocholine were separated on a cation exchange chromatography column (Nucleosil SCX, Skandinaviska Genentch AB, Sweden) by HPLC and ICP-MS (7700x Agilent), as described previously (Reid et al, 2020;Xie et al, 2006;Torbøl Pedersen et al, 2020). The average LOD of 10 analyses were 0.27 μg/L for arsenobetaine and 0.28 μg/L for arsenocholine.…”

Navigating a Two-Way Street: Metal Toxicity and the Human Gut Microbiome

“…A study led by Seth Walk, an associate professor of microbiology and cell biology at Montana State University, found that a healthy human microbiome transferred into germ-free As3mt knockout mice via fecal transplant completely protected the mice against the lethal effects of acute iAs exposure. 48 This was partially due to the activity of the arsenic methyltransferase ( ArsM ) gene cluster 58 —the bacterial analog of the human AS3MT gene—in the common gut microbe Faecalibacterium prausnitzii. 48 …”

“…The geologic contamination of drinking water has existed for a very long time, whereas human-caused increases in atmospheric Hg are more recent. This difference, says Broberg, may explain the evolution of the AS3MT defense system in many species 58 , 75 , 76 and the lack of an analogous MeHg system. “I find it very interesting that the same arsenic defense system exists in bacteria and humans because this is not the case for many other environmental chemicals,” she says.…”