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Eukaryotic Cell, March 2007, p. 495-504, Vol. 6, No. 3
1535-9778/07/$08.00+0     doi:10.1128/EC.00191-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae{triangledown}

Ulrich Mühlenhoff,1 Mathias J. Gerl,2,{dagger} Birgit Flauger,2 Heike M. Pirner,2 Sandra Balser,2 Nadine Richhardt,1 Roland Lill,1 and Jürgen Stolz2*

Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35033 Marburg, Germany,1 Lehrstuhl für Zellbiologie und Pflanzenphysiologie, Universität Regensburg, Universitätsstrasse 31, 93040 Regensburg, Germany2

Received 17 June 2006/ Accepted 15 January 2007

The yeast Saccharomyces cerevisiae is able to use some biotin precursors for biotin biosynthesis. Insertion of a sulfur atom into desthiobiotin, the final step in the biosynthetic pathway, is catalyzed by biotin synthase (Bio2). This mitochondrial protein contains two iron-sulfur (Fe/S) clusters that catalyze the reaction and are thought to act as a sulfur donor. To identify new components of biotin metabolism, we performed a genetic screen and found that Isa2, a mitochondrial protein involved in the formation of Fe/S proteins, is necessary for the conversion of desthiobiotin to biotin. Depletion of Isa2 or the related Isa1, however, did not prevent the de novo synthesis of any of the two Fe/S centers of Bio2. In contrast, Fe/S cluster assembly on Bio2 strongly depended on the Isu1 and Isu2 proteins. Both isa mutants contained low levels of Bio2. This phenotype was also found in other mutants impaired in mitochondrial Fe/S protein assembly and in wild-type cells grown under iron limitation. Low Bio2 levels, however, did not cause the inability of isa mutants to utilize desthiobiotin, since this defect was not cured by overexpression of BIO2. Thus, the Isa proteins are crucial for the in vivo function of biotin synthase but not for the de novo synthesis of its Fe/S clusters. Our data demonstrate that the Isa proteins are essential for the catalytic activity of Bio2 in vivo.

* Corresponding author. Mailing address: Lehrstuhl für Zellbiologie und Phlanzenphysiologie, Universität Regensburg, Universitätsstrasse 31, 93040 Regensburg, Germany. Phone: 49 941 943 3005. Fax: 49 941 943 3352. E-mail: juergen.stolz{at}biologie.uni-regensburg.de.

{triangledown} Published ahead of print on 26 January 2007.

{dagger} Present address: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

Eukaryotic Cell, March 2007, p. 495-504, Vol. 6, No. 3
1535-9778/07/$08.00+0     doi:10.1128/EC.00191-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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