Comparative Genomics and Evolution of Molybdenum Utilization

Abstract

The trace element molybdenum (Mo) is the catalytic component of important enzymes involved in global nitrogen, sulfur, and carbon metabolism in both prokaryotes and eukaryotes. With the exception of nitrogenase, Mo is complexed by a pterin compound thus forming the biologically active molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. The physiological roles and biochemical functions of many molybdoenzymes have been characterized. However, our understanding of the occurrence and evolution of Mo utilization is limited. This article focuses on recent advances in comparative genomics of Mo utilization in the three domains of life. We begin with a brief introduction of Mo transport systems, the Moco biosynthesis pathway, the role of posttranslational modifications, and enzymes that utilize Mo. Then, we proceed to recent computational and comparative genomics studies of Mo utilization, including a discussion on novel Moco-binding proteins that contain the C-terminal domain of the Moco sulfurase and that are suggested to represent a new family of molybdoenzymes. As most molybdoenzymes need additional cofactors for their catalytic activity, we also discuss interactions between Mo metabolism and other trace elements and finish with an analysis of factors that may influence evolution of Mo utilization.

Fig. 1. Biosynthesis of molybdenum cofactor

The pathway of Moco synthesis can be divided into three or four steps. (A) Biosynthesis of molybdenum cofactor in prokaryotes. (B) Biosynthesis of molybdenum cofactor in eukaryotes. The proteins from E. coli and A. thaliana catalyzing the respective steps are depicted and their names are given. MGD, molybdopterin guanine dinucleotide.

Fig. 2. Distribution of Mo/W transporters in Mo-utilizing organisms in bacteria and archaea

Three classes of high-affinity Mo/W ABC transport systems are known: ModABC, WtpABC and TupABC.

Fig. 3. Distribution of molybdoenzymes in Mo-utilizing organisms in the three domains of life

SO, sulfite oxidase; XO, xanthine oxidase; DMSOR, dimethylsulfoxide reductase, AOR, aldehyde:ferredoxin oxidoreductase. 100% represents all Mo-utilizing organisms in each domain of life.

Fig. 4. Domain organizations of Moco sulfurase and novel Moco-containing proteins

Different domains are shown by different colors. MOSC, C-terminal domain of the eukaryotic Moco sulfurase.

Fig. 5. Occurrence of mARC/YcbX and YiiM proteins in different phyla in bacteria and eukaryotes

(A) Bacteria; (B) Eukaryotes. Moco (+), organisms containing the Moco biosynthesis pathway.

Fig. 6. Novel fusion forms of MOSC-containing proteins

(A) New fusions of YiiM. (B) New fusions of mARC/YcbX. Different domains are shown by different colors.

Fig. 7. Phylogenetic tree of MOSC-containing proteins

Measurement of a distance for the branch length is indicated. Four MOSC-containing protein families are included: Moco sulfurase, mARC/YcbX, YiiM and MOSC-like protein.

Fig. 8. Relationship between environmental factors and the Mo utilization trait

Organisms were split into two groups: Mo (+), i.e. containing the Mo utilization trait; Mo (−), i.e. lacking Mo utilization. (A) Habitat. (B) Different host-associated life styles. (C) Relationship between parasitic lifestyles and Mo utilization trait in eukaryotes.