Table of Contents
Advances in Biology
Volume 2014, Article ID 808569, 21 pages
Review Article

The Biosynthesis of the Molybdenum Cofactor in Escherichia coli and Its Connection to FeS Cluster Assembly and the Thiolation of tRNA

Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany

Received 16 January 2014; Accepted 28 March 2014; Published 29 April 2014

Academic Editor: Paul Rösch

Copyright © 2014 Silke Leimkühler. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The thiolation of biomolecules is a complex process that involves the activation of sulfur. The L-cysteine desulfurase IscS is the main sulfur mobilizing protein in Escherichia coli that provides the sulfur from L-cysteine to several important biomolecules in the cell such as iron sulfur (FeS) clusters, molybdopterin (MPT), thiamine, and thionucleosides of tRNA. Various proteins mediate the transfer of sulfur from IscS to various biomolecules using different interaction partners. A direct connection between the sulfur-containing molecules FeS clusters, thiolated tRNA, and the molybdenum cofactor (Moco) has been identified. The first step of Moco biosynthesis involves the conversion of 5′GTP to cyclic pyranopterin monophosphate (cPMP), a reaction catalyzed by a FeS cluster containing protein. Formed cPMP is further converted to MPT by insertion of two sulfur atoms. The sulfur for this reaction is provided by the L-cysteine desulfurase IscS in addition to the involvement of the TusA protein. TusA is also involved in the sulfur transfer for the thiolation of tRNA. This review will describe the biosynthesis of Moco in E. coli in detail and dissects the sulfur transfer pathways for Moco and tRNA and their connection to FeS cluster biosynthesis.