Bacterial molybdoenzymes: old enzymes for new purposes

Abstract

Molybdoenzymes are widespread in eukaryotic and prokaryotic organisms where they play crucial functions in detoxification reactions in the metabolism of humans and bacteria, in nitrate assimilation in plants and in anaerobic respiration in bacteria. To be fully active, these enzymes require complex molybdenum-containing cofactors, which are inserted into the apoenzymes after folding. For almost all the bacterial molybdoenzymes, molybdenum cofactor insertion requires the involvement of specific chaperones. In this review, an overview on the molybdenum cofactor biosynthetic pathway is given together with the role of specific chaperones dedicated for molybdenum cofactor insertion and maturation. Many bacteria are involved in geochemical cycles on earth and therefore have an environmental impact. The roles of molybdoenzymes in bioremediation and for environmental applications are presented.

Chaperones in maturation of molybdoenzymes: Why specific is better than general?

“…Indeed we can distinguish those belonging to LUCA from those more recently evolved, we can classify them into 3 families according to the modification of the basic form of the molybdenum cofactor and we now know the major steps of their biosynthesis. [2][3][4][5] In the 3 domains of life, molybdoenzymes are essential. Indeed, molybdoenzymes are involved in detoxification processes and in bacterial anaerobic respiration.…”

“…12,13 To study the maturation of molybdoenzymes of the DMSO reductase family, we have chosen to dissect the maturation process of TorA. 5 TorA is a trimethylamine oxide (TMAO) reductase and the terminal electron acceptor of the Tor respiratory system present in bacteria, especially in aquatic Proteobacteria. TorA turned out to be an exquisite model because it is a simple enzyme with respect of its composition, a soluble monomer containing the molybdenum cofactor (bis-molybdopterin guanine dinucleotide cofactor (bisMGD) form) as sole prosthetic group.…”

“…The study of this basic model led to establish the various steps of molybdoenzyme maturation that were then also studied in other molybdoenzymes and that are extensively described in various recent reviews. 5,12 TorA is a protein of about 90 kDa and its fold is organized into 4 domains with only the fourth C-terminal domain being made with a continuous amino acid stretch and 2 domains mainly involved in the binding of the cofactor. 14 Moreover, the cofactor is deeply buried at the extremity of a funnel-like deep depression in the core of the enzyme.…”

“…The latter point shared by the numerous enzymes of the DMSO reductase family crystallized so far was also observed in solved crystal structures of enzymes of the XO family members. 4,5 The maturation process of enzymes of the XO family has also been well studied, with the xanthine dehydrogenase of Rhodobacter capsulatus as a model. Members of these family are multimeric complexes containing either the basic Mo-MPT or the MCD (molybdopterin cytosine dinucleotide) form of the molybdenum cofactor and also iron sulfur clusters and FAD.…”

“…ANA-3 compared to that of other bacteria. 5,16 This observation raises the question of why for some enzymes a dedicated chaperone is required and why some others can insert their cofactor without the support of accessory proteins. The fact that a minimal amount of TorA can be matured in the absence of the chaperone TorD indicates that the maturation process can be done even without specific chaperone, although this appears not to be the rule.…”