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Review
. 2024 Jun;1871(5):119731.
doi: 10.1016/j.bbamcr.2024.119731. Epub 2024 Apr 16.

Shared functions of Fe-S cluster assembly and Moco biosynthesis

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Free article
Review

Shared functions of Fe-S cluster assembly and Moco biosynthesis

Muhammad Abrar Hasnat et al. Biochim Biophys Acta Mol Cell Res. 2024 Jun.
Free article

Abstract

Molybdenum cofactor (Moco) biosynthesis is a complex process that involves the coordinated function of several proteins. In the recent years it has become evident that the availability of Fe-S clusters play an important role for the biosynthesis of Moco. First, the MoaA protein binds two [4Fe-4S] clusters per monomer. Second, the expression of the moaABCDE and moeAB operons is regulated by FNR, which senses the availability of oxygen via a functional [4Fe-4S] cluster. Finally, the conversion of cyclic pyranopterin monophosphate to molybdopterin requires the availability of the L-cysteine desulfurase IscS, which is an enzyme involved in the transfer of sulfur to various acceptor proteins with a main role in the assembly of Fe-S clusters. In this review, we dissect the dependence of the production of active molybdoenzymes in detail, starting from the regulation of gene expression and further explaining sulfur delivery and Fe-S cluster insertion into target enzymes. Further, Fe-S cluster assembly is also linked to iron availability. While the abundance of selected molybdoenzymes is largely decreased under iron-limiting conditions, we explain that the expression of the genes is dependent on an active FNR protein. FNR is a very important transcription factor that represents the master-switch for the expression of target genes in response to anaerobiosis. Moco biosynthesis is further directly dependent on the presence of ArcA and also on an active Fur protein.

Keywords: FNR; FeS clusters; Gene regulation; Iron; Molybdenum cofactor.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Silke Leimkuehler reports financial support and administrative support were provided by Deutsche Forschungsgemeinschaft. Silke Leimkuehler reports financial support was provided by German Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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