Description | Title: Mapping Biochemical Space to Search for Life Beyond Earth Abstract: A fundamental goal of biology is to understand the rules behind life’s use of chemical space. Established work focuses on why life uses chemistry that it does. Given the enormous scope of possible chemical space, I postulate that it is equally important to ask why life largely avoids certain areas of chemical space. I will illustrate such life’s choices, preferences and limitations with several examples identified by careful database development, “big data” analysis and cheminformatics approaches. The nitrogen-sulfur bond is a prime example as it rarely appears in natural molecules, despite the very rich N-S bond chemistry applied in various branches of industry (e.g., industrial materials, agrochemicals, pharmaceuticals). I find that out of hundreds of thousands of known, unique, compounds made by life, only about 100 contain N-S bonds. Furthermore, the limited number of N-S bond-containing molecules that life produces appear to fall into a few very distinctive structural groups. One may think that industrial processes are unrelated to biochemistry because of a greater possibility of solvents, catalysts, and temperatures available to industry than to the cellular environment. However, the fact that life does rarely make N-S bonds, from the plentiful precursors available, and has evolved the ability to do so independently several times, suggests that the restriction on life’s use of N-S chemistry is not in its synthesis. I present a hypothesis to explain life’s extremely limited usage of the N-S bond: that the N-S bond chemistry is incompatible with essential segments of biochemistry, specifically with thiols. I support the hypothesis by 1] a quantitative analysis of the occurrence of N-S bond-containing natural products and 2] reactivity experiments between selected N-S compounds and key biological molecules. This work provides an example of a reason why life nearly excludes a distinct region of chemical space. Combined with future examples this potentially new field of research may provide fresh insight into life’s evolution through chemical space and its origin and early evolution. |
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