Methane, arsenic, selenium and the origins of the DMSO reductase family

Abstract

Mononuclear molybdoenzymes of the dimethyl sulfoxide reductase (DMSoR) family catalyze a number of reactions essential to the carbon, nitrogen, sulfur, arsenic, and selenium biogeochemical cycles. these enzymes are also ancient, with many lineages likely predating the divergence of the last universal common ancestor into the Bacteria and Archaea domains. We have constructed rooted phylogenies for over 1,550 representatives of the DMSOR family using maximum likelihood methods to investigate the evolution of the arsenic biogeochemical cycle. the phylogenetic analysis provides compelling evidence that formylmethanofuran dehydrogenase B subunits, which catalyze the reduction of co 2 to formate during hydrogenotrophic methanogenesis, constitutes the most ancient lineage. our analysis also provides robust support for selenocysteine as the ancestral ligand for the Mo/W atom. finally, we demonstrate that anaerobic arsenite oxidase and respiratory arsenate reductase catalytic subunits represent a more ancient lineage of DMSoRs compared to aerobic arsenite oxidase catalytic subunits, which evolved from the assimilatory nitrate reductase lineage. this provides substantial support for an active arsenic biogeochemical cycle on the anoxic Archean earth. our work emphasizes that the use of chalcophilic elements as substrates as well as the Mo/W ligand in DMSORs has indelibly shaped the diversification of these enzymes through deep time. Ubiquitous in Archaea and Bacteria, mononuclear molybdoenzymes of the dimethyl sulfoxide reductase (DMSOR) family are believed to have been core components of the first anaerobic respiratory chains, and thus present at life's origins 1-4. Reactions catalyzed by these enzymes are integral components of the carbon, nitrogen, and sulfur biogeochemical cycles, as well as the biogeochemical cycles of arsenic and selenium 5 , and likely antimony 6,7. The family, which has been defined by the presence of a mononuclear molybdopterin or tungstopterin bis(pyranopterin guanine dinucleotide) (Mo/W-bisPGD) co-factor 5 , was named after DMSO reductases, the first members of the family to be well-characterized 8-12. As more representatives of the family were discovered and characterized, many were found to be heterotrimeric complexes, consisting of the catalytic subunit (the Mo/W-bisPGD-harboring subunit), an electron transfer subunit with as many as four [Fe-S] clusters, and a membrane anchoring subunit that tethers the complex to the membrane and transfers electrons to or from the membrane quinone pool. Thus, members of the family have also been referred to as Complex Iron-Sulfur Molybdoenzymes (CISMs) 13. The catalytic subunit may additionally have a twin-arginine translocation motif for export to the periplasm, and a [4Fe-4S] or [3Fe-4S] iron-sulfur cluster 13,14. It has been noted, however, that these characteristics are not uniform across the family, as there are numerous examples where one or more of the associated subunits are missing, or the catalytic subunits associate with different subunits altoget...

Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

“…All DMSOR family enzymes contain a Mo-bisPGD cofactor (Figure 5), and the four dithiolene sulfur atoms of the two cofactor molecules coordinate the Mo atom, together with an oxo-or a sulfido-group and an amino acid ligand (Johnson et al, 1990;Leimkühler et al, 2011;Leimkühler and Iobbi-Nivol, 2016;Kaufmann et al, 2018;Leimkühler, 2020). Different amino acid ligands including serine, cysteine, selenocysteine, and aspartate have been identified in DMSOR enzymes and their distribution largely coincides with three major phylogenetic groups identified in various studies: type I enzymes (e.g., NapAB nitrate reductase and FdnGHI formate dehydrogenase) contain a cysteine or selenocysteine ligand; type II enzymes, such as the heterotrimeric NarGHI nitrate reductase, the DmsABC DMSO reductase and the EbdABC ethylbenzene dehydrogenase, have an aspartate amino acid ligand; and the type III Dor/Tor-type S-and N-oxide reductases typically have a serine amino acid ligand (McDevitt et al, 2002;Grimaldi et al, 2013;Kappler and Schäfer, 2014;Wells et al, 2020). The AioAB arsenite oxidase is an outlier in this classification system, because of the absence of an amino acid ligand to the Mo; however, the AioAB amino acid sequence is most closely related to type I enzymes (McEwan et al, 2002;Warelow et al, 2013).…”

“…The AioAB arsenite oxidase is an outlier in this classification system, because of the absence of an amino acid ligand to the Mo; however, the AioAB amino acid sequence is most closely related to type I enzymes (McEwan et al, 2002;Warelow et al, 2013). Crystal structures as well as functional and spectroscopic properties are available for many of these enzymes and have been reviewed previously (Rothery et al, 2008;Magalon et al, 2011Magalon et al, , 2017Gonzalez et al, 2013;Grimaldi et al, 2013;Hille et al, 2014;Wells et al, 2020).…”

“…Currently, the so-called mononuclear Mo/W enzymes, which contain a single Mo or W atom complexed by an organic pyranopterin (PPT) cofactor at their active site, are the most abundant group of Mo/W-containing enzymes (Magalon et al, 2011;Iobbi-Nivol and Leimkühler, 2013;Hille et al, 2014;Rothery and Weiner, 2015;Hagen, 2017). Mo/W enzymes are evolutionarily old and likely already existed in the last universal common ancestor (Lebrun et al, 2003;Zhang and Gladyshev, 2008;Schoepp-Cothenet et al, 2012;Nitschke and Russell, 2013;Mayr et al, 2020;Wells et al, 2020). As a result, they are found in all domains of life and are particularly abundant in bacteria, where more than 50 distinct types of enzymes have been identified (Leimkühler and Iobbi-Nivol, 2016;Maia et al, 2017), and physiological functions range from sulfur compound oxidation, degradation of aromatic compounds to supporting anaerobic respiration in bacteria (Hille et al, 2014;Maia et al, 2017).…”

Gating of Substrate Access and Long-Range Proton Transfer in Escherichia coli Nitrate Reductase A: The Essential Role of a Remote Glutamate Residue

“…From an evolutionary point of view, Nar is one of the few Mo/W-bisPGD enzymes that were proposed to have been present in LUCA (3,13). Phylogenetic analysis places Nar in a major clade sharing Asp/Oxygen as Mo coordinating ligands (1,14) together with ethylbenzene dehydrogenase and perchlorate reductase (Pcr) for which X-ray structural data are also available (15,16). Moreover, Nar is an attractive model due to its high stability, oxygen insensitivity and the wealth of biochemical, spectroscopic and structural data available on the enzyme (10,(17)(18)(19)(20)(21).…”

Anaerobic Sulfur Oxidation Underlies Adaptation of a Chemosynthetic Symbiont to Oxic-Anoxic Interfaces

“…Besides nitrate respiration, “ Ca . T. oneisti” may also utilize polysulfide or thiosulfate as a terminal electron acceptor under AS conditions, since we observed an upregulation of all genes encoding either a respiratory polysulfide reductase or a thiosulfate reductase ( psrA/phsA , psrB/phsB , prsC/phsC ; dimethyl sulfoxide [DMSO] reductase family, classification based on reference 36 ). Concerning other anaerobic electron acceptors, the symbiont has the genetic potential to carry out fumarate reduction ( frdABCD genes; Fig.…”