title: The sulfur carrier protein TusA has a pleiotropic role in Escherichia coli that also affects molybdenum cofactor biosynthesis.
abstract: The Escherichia coli L-cysteine desulfurase IscS mobilizes sulfur from L-cysteine for the synthesis of several biomolecules such as iron-sulfur (FeS) clusters, molybdopterin, thiamin, lipoic acid, biotin, and the thiolation of tRNAs. The sulfur transfer from IscS to various biomolecules is mediated by different interaction partners (e.g. TusA for thiomodification of tRNAs, IscU for FeS cluster biogenesis, and ThiI for thiamine biosynthesis/tRNA thiolation), which bind at different sites of IscS. Transcriptomic and proteomic studies of a ΔtusA strain showed that the expression of genes of the moaABCDE operon coding for proteins involved in molybdenum cofactor biosynthesis is increased under aerobic and anaerobic conditions. Additionally, under anaerobic conditions the expression of genes encoding hydrogenase 3 and several molybdoenzymes such as nitrate reductase were also increased. On the contrary, the activity of all molydoenzymes analyzed was significantly reduced in the ΔtusA mutant. Characterization of the ΔtusA strain under aerobic conditions showed an overall low molybdopterin content and an accumulation of cyclic pyranopterin monophosphate. Under anaerobic conditions the activity of nitrate reductase was reduced by only 50%, showing that TusA is not essential for molybdenum cofactor biosynthesis. We present a model in which we propose that the direction of sulfur transfer for each sulfur-containing biomolecule is regulated by the availability of the interaction partner of IscS. We propose that in the absence of TusA, more IscS is available for FeS cluster biosynthesis and that the overproduction of FeS clusters leads to a modified expression of several genes.
authors.affiliation: Institute of Biochemistry and Biology, Department of Molecular Enzymology, University of Potsdam, 14476 Potsdam, Germany.
authors.forename: Jan-Ulrik
authors.initials: JU
authors.lastname: Dahl
authors.forename: Christin
authors.initials: C
authors.lastname: Radon
authors.forename: Martin
authors.initials: M
authors.lastname: Bühning
authors.forename: Manfred
authors.initials: M
authors.lastname: Nimtz
authors.forename: Lars I
authors.initials: LI
authors.lastname: Leichert
authors.forename: Yann
authors.initials: Y
authors.lastname: Denis
authors.forename: Cécile
authors.initials: C
authors.lastname: Jourlin-Castelli
authors.forename: Chantal
authors.initials: C
authors.lastname: Iobbi-Nivol
authors.forename: Vincent
authors.initials: V
authors.lastname: Méjean
authors.forename: Silke
authors.initials: S
authors.lastname: Leimkühler
mesh_terms: D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D003067:Coenzymes / Q000096:biosynthesis*; D015180:Electrophoresis, Gel, Two-Dimensional; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008667:Metalloproteins / Q000096:biosynthesis*; D008954:Models, Biological; D000090006:Molybdenum Cofactors; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011621:Pteridines; D012343:RNA, Transfer / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D013455:Sulfur / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods; D014158:Transcription, Genetic
chemical_list: D013437:Carbon-Sulfur Lyases; D003067:Coenzymes; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; D012343:RNA, Transfer; D013438:Sulfhydryl Compounds; D013440:Sulfides; D013455:Sulfur; C551794:TusA protein, E coli; C051552:persulfides; C022261:molybdopterin; C080546:cysteine desulfurase