The role of FeS clusters for molybdenum cofactor biosynthesis and molybdoenzymes in bacteria

Abstract

Molybdenum is the only second row transition metal essential for biological systems, which is biologically available as molybdate ion. In eukarya, bacteria and archaea, molybdenum is bound to either to a tricyclic pyranopterin, thereby forming the molybdenum cofactor (Moco), or in some bacteria to the FeS cluster based iron-molybdenum cofactor (FeMoco), which forms the active site of nitrogenase. To date more than 50 Moco-containing enzymes have been purified and biochemically or structurally characterized. The physiological role of molybdenum in these enzymes is fundamental to organisms, since the reactions include the catalysis of key steps in carbon, nitrogen and sulfur metabolism. The catalyzed reactions are in most cases oxo-transfer reactions or the hydroxylation of carbon centers. The biosynthesis of Moco has been intensively studied, in addition to its insertion into molybdoenzymes. In particular, a link between the biosynthesis and maturation of molybdoenzymes and the biosynthesis and distribution of FeS clusters has been identified in the last years: 1) The synthesis of the first intermediate in Moco biosynthesis requires an FeS-cluster containing protein, 2) The sulfurtransferase for the dithiolene group in Moco is common also for the synthesis of FeS clusters, thiamin and thiolated tRNAs, 3) the modification of the active site with a sulfur atom additionally involves a sulfurtransferase, 4) most molybdoenzymes in bacteria require FeS clusters as additional redox active cofactors. In this review we will focus on the biosynthesis of the molybdenum cofactor in bacteria, its modification and insertion into molybdoenzymes, with an emphasis to its link to FeS cluster biosynthesis and sulfur transfer.

Comparative Analysis of Extremely Thermophilic Caldicellulosiruptor Species Reveals Common and Unique Cellular Strategies for Plant Biomass Utilization

“…Note that the molybdenum cofactor biosynthesis proteins upregulated in C. saccharolyticus (Fig. 4, D) also contain Fe-S clusters (38). In contrast, homologs within the sulfate assimilation locus (Fig.…”

Iron-Dependent Regulation of Molybdenum Cofactor Biosynthesis Genes in Escherichia coli

“…It has been reported in recent years that iron also represents an important factor for Moco biosynthesis, both at the level of transcription and the level of activity of the proteins involved in its synthesis (12,33,41). It is known that the production of Moco is directly dependent on a functional Fe-S cluster assembly by the activity of the MoaA protein, which binds two [4Fe-4S] clusters per monomer (40). Further, the transcription of the moaABCDE and moeAB operons depends on FNR as a transcriptional factor that binds a functional [4Fe-4S] cluster only under anaerobic conditions (33,66).…”

“…However, apart from the dependence on functional [4Fe-4S] clusters being present in the FNR protein, a regulation of Moco biosynthesis by cellular iron levels has not been investigated in the past. This is surprising, since it has become evident that Moco biosynthesis depends on Fe-S clusters or components of the Fe-S cluster assembly machinery at several levels (40). In the first step of Moco biosynthesis, the MoaA protein requires two [4Fe-4S] clusters for activity (12,41).…”

“…In the first step of Moco biosynthesis, the MoaA protein requires two [4Fe-4S] clusters for activity (12,41). Further, most molybdoenzymes in E. coli harbor numerous Fe-S clusters that are involved in intramolecular electron transfer reactions, which are essential for the activity of the enzymes (4,40). In E. coli two major systems for the assembly of Fe-S clusters have been identified, namely, the iron sulfur cluster (ISC) system and the sulfur mobilization (SUF) system (42,43).…”

Bacterial Electron Transfer Chains Primed by Proteomics

“…The pathway is named after two adjacent arginines that typically are located about 20 positions after the translation start. Preassembly within the cytoplasm may include the insertion of iron-sulphur clusters synthesised by the Suf and ISC systems (Blanc, Gerez, & Ollagnier de Choudens, 2015;Kim, Bothe, Alderson, & Markley, 2015;Kim, Jang, et al, 2015;Wayne Outten, 2015;Yokoyama & Leimkühler, 2015) or of the molybdopterin cofactor, which is the catalytic heart of a wide variety of respiratory enzymes, including formate dehydrogenase and nitrate reductase (Grimaldi, Schoepp-Cothenet, Ceccaldi, Guigliarelli, & Magalon, 2013). Translation at the ribosomes and transport through the membrane can be intimately coupled by action of the signal recognition particle, trigger factor and of the DnaK and GroeEL protein-folding apparatus (Castani e-Cornet, Bruel, & Genevaux, 2014;Saraogi & Shan, 2014).…”