Coordination Funds

铁硫（FeS）中心是所有生命形式中必不可少的蛋白质辅因子。它们参与了许多关键的生物过程，包括呼吸，光合作用，氮，硫，碳和氢的代谢，抗生素的生物合成，基因调控，蛋白质翻译，复制和DNA修复，保护免受氧化剂和神经传递。特别是，FeS中心不仅作为酶的辅助因子参与催化和电子转移，而且在复杂的含金属辅助因子的生物合成中也是不可或缺的。一个突出的例子是2001年发现的依赖于自由基/ s -腺苷蛋氨酸的酶家族。该家族的成员在金属中心的生物合成中发挥重要作用，如氮酶的铁钼辅助因子（FeMoco）、各种钼酶的钼辅助因子（Moco）、[Fe-Fe]-和[Fe]-氢化酶的活性位点以及血红素、铁和氯的四吡啶辅助因子。尽管最近在金属酶研究方面取得了根本性的突破，但很明显，对单个酶的研究必须转变为更广泛的活细胞背景，在活细胞中，这些迷人的金属辅因子的生物合成、功能和分解以动态的方式耦合在一起。研究发现，各种生物合成途径通过复杂的串扰机制紧密相连，该机制涉及对不同金属离子的生物利用度的依赖，特别是钼、铁、钨和镍。目前缺乏这种相互作用网络的知识是由于金属辅因子生物合成的纯粹复杂性，涉及（遗传）调控和（化学）金属中心组装。最近开创性的技术发展使得在细胞背景下对fes依赖性酶的组装，生物合成和催化进行了详细的研究，开辟了研究金属酶的新时代。这些研究不仅对理解基本的细胞过程很重要，而且也是全面了解金属相关人类疾病背后的复杂生物合成和金属酶催化机制的先决条件。金属酶的这些关键特征只能在细胞环境中实现。在细胞的基础上理解金属离子的串扰需要多学科的合作方法，从分子生物学、无机化学、生物化学、细胞生物学、结构生物学到理论和光谱学。在SPP计划研究新的酶的机制，创新的模式复合物和新的生物发生途径在生物体内金属酶的生理背景下。

Iron-sulfur (FeS) centers are essential protein cofactors in all forms of life. They are involved in many of the key biological processes including respiration, photosynthesis, metabolism of nitrogen, sulfur, carbon and hydrogen, biosynthesis of antibiotics, gene regulation, protein translation, replication and DNA repair, protection from oxidizing agents, and neurotransmission. In particular, FeS centers are not only involved as enzyme cofactors in catalysis and electron transfer, but they are also indispensable for the biosynthesis of complex metal-containing cofactors. A prominent example is represented by the family of radical/S-adenosylmethionine-dependent enzymes, which were discovered in 2001. Members of this family play essential roles in the biosynthesis of metal centers as complex as the iron-molybdenum cofactor (FeMoco) of nitrogenase, the molybdenum cofactor (Moco) of various molybdoenzymes, the active sites of [Fe-Fe]- and [Fe]-hydrogenases and the tetrapyrrole cofactors of hemes, corrins and chlorins. In spite of the recent fundamental breakthroughs in metalloenzyme research, it has become evident that studies on single enzymes have to be transformed into the broader context of a living cell where biosynthesis, function, and disassembly of these fascinating metal cofactors are coupled in a dynamic fashion. The various biosynthetic pathways were found to be tightly interconnected through a complex crosstalk mechanism that involves the dependence on the bio-availability of distinct metal ions, in particular molybdenum, iron, tungsten and nickel. The current lack of knowledge of such interaction networks is due to the sheer complexity of the metal cofactor biosynthesis with regard to both the (genetic) regulation and (chemical) metal center assembly. Recent pioneering technical developments allowed the detailed investigation of the assembly, biosynthesis and catalysis of FeS-dependent enzymes in a cellular context, opening up a new era in studying metalloenzymes. Such studies are not only important for understanding fundamental cellular processes but they are also a prerequisite for providing a comprehensive view of the complex biosynthesis and the catalytic mechanism of metalloenzymes that underlie metal-related human diseases. These key features of metalloenzymes can only be implemented in a cellular context. Understanding the crosstalk of metal ions on a cellular basis requires multidisciplinary cooperative approaches that span the entire range from molecular biology, inorganic chemistry, biochemistry, cell biology, and structural biology to theory and spectroscopy. In the SPP it is planned to study novel enzyme mechanisms, innovative model complexes, and new biogenesis pathways in the physiological context of metalloenzymes in living organisms.