Cell-free synthesis of iron-sulfur clusters for artificial cells

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Artificial cells are mimics of living cells built in the laboratory with DNA, protein, and lipids. Although building such systems in the laboratory is more challenging than engineering living cells, there are numerous benefits. First, there is arguably no better way to understand how biology works than to try to build biological systems from component parts. Further, we can intentionally put in the parts of biology that are advantageous when building a cellular mimic from scratch while simultaneously leaving out that problematic parts of biology. For example, non-living cellular mimics, i.e. artificial cells, can be built to not replicate, which completely removes the fear of losing control of the system. There can be no long-term ecological consequences, because once the artificial cells fall apart, the environment returns to its prior state. We have built artificial cells that can chemically communicate with and control natural living cells. Such technologies have numerous potential applications, from cleaning our environment of pollutants to treating debilitating diseases and infections. However, the state-of-the-art in artificial cells are not long-lived. That is, the artificial cells are active for a couple of hours then degrade. Here, we intend to give the artificial cells metabolism so that the artificial cells can function long enough to be useful. To do so, we need to learn how to build the components of metabolism outside of a living cell. We will start by tackling the synthesis of one of the more complex parts of metabolism, which is the synthesis of iron-sulfur proteins. Iron-sulfur clusters are ancient, inorganic arrangements of atoms that mediate much of the chemistry that keeps cells alive. By exploiting our expertise in the synthesis of iron-sulfur clusters and in in vitro genetics, we will develop a genetically encoded pathway within artificial cells that synthesizes the iron-sulfur proteins of metabolism. These proteins will then be combined with other genetically encoded factors to begin giving artificial cells a rudimentary form of metabolism. Additionally, we will exploit the developed pathways to generate new types of catalysts capable of producing biofuels. Both iron-sulfur protein and iron-sulfur peptide catalysts will be pursued for potential applications in industry. We are one of the leaders in the synthesis of artificial cells. This project will help us consolidate our position, potentially giving rise to the generation of new technologies and companies. Additionally, this project will enrich our understanding of the chemical foundations of biology.