Roland Lill

Research area

The Lill group focuses on the molecular mechanisms of the biosynthesis of iron-sulfur (Fe/S) clusters in eukaryotes (see Lill, R. (2009) Nature 460, 831-838). These substances act as inorganic cofactors of proteins that play a role in, e. g., ribosomal protein translation, DNA synthesis and repair, the modification of nucleic acids, the conversion of metabolites, or the transfer of electrons in biochemical reactions. Eukaryotic Fe/S protein biosynthesis involves more than 30 proteins in mitochondria and cytosol. Mitochondrial Fe/S proteins require the iron-sulfur cluster (ISC) assembly machinery which was inherited from bacteria during evolution (see Fig.). Cytosolic and nuclear Fe/S protein assembly also depends on the function of this machinery, yet additionally requires the mitochondrial ISC export apparatus and the cytosolic iron-sulfur protein assembly (CIA) machinery.

 

Research project within SYNMIKRO

There is a growing interest in the use of Fe/S proteins for biosynthetic approaches in the production of compounds such as alcohols or isoprene derivatives, which serve as versatile starting materials for drugs, cosmetics and fine chemicals. In these approaches, new artificial biosynthetic pathways including Fe/S proteins are introduced into bacteria or yeast for targeted enzymatic synthesis of the desired molecules. Since the assembly of heterologous iron-sulfur proteins frequently occurs inefficiently, we try to uncover the molecular mechanisms of Fe/S protein biogenesis, and to identify and characterize all proteins involved. This approach will provide a more accurate understanding of the assembly processes, and in turn will lead to sophisticated methods and tricks to increase the activity of the heterologously expressed Fe/S proteins in the synthetically constructed pathways. For example, our studies address the question of how [2Fe-2S] proteins are assembled in the yeast cytosol. An investigation of the protein Dre2 with a [2Fe-2S] cluster revealed that the above-mentioned CIA machinery is not needed for the maturation of this Fe/S protein. Similar observations were made for other [2Fe-2S] proteins (see Fig.). We therefore address the question of which assembly proteins are involved in the maturation of cytosolic [2Fe-2S] proteins, we investigate the molecular mechanisms of the maturation process, and we analyze how this process differs from that of [4Fe-4S] proteins. Our insights will be useful for future biosynthetic purposes.