1 Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA.
2 Rufus Scientific , Melbourn, UK.
Astrobiology. 2019 Apr;19(4):579-613. doi: 10.1089/ast.2018.1831. Epub 2018 Nov 22.
A fundamental goal of biology is to understand the rules behind life's use of chemical space. Established work focuses on why life uses the chemistry that it does. Given the enormous scope of possible chemical space, we postulate that it is equally important to ask why life largely avoids certain areas of chemical space. 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). We find that, out of more than 200,000 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 appears 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. We 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. We support our 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.
生物学的一个基本目标是理解生命利用化学空间背后的规律。已有的研究工作主要关注生命为什么会使用它所使用的化学物质。鉴于化学空间的范围非常广泛，我们假设同样重要的是要问为什么生命在很大程度上避免了某些化学空间区域。氮硫键就是一个很好的例子，尽管在各个工业领域（例如工业材料、农用化学品、制药）都应用了丰富的 N-S 键化学，但它在天然分子中很少出现。我们发现，在生命制造的 20 多万种已知的、独特的化合物中，只有约 100 种含有 N-S 键。此外，生命产生的含 N-S 键的分子数量有限，似乎属于几个非常独特的结构群。人们可能认为工业过程与生物化学无关，因为工业环境中溶剂、催化剂和温度的可能性更大。然而，由于有大量的前体可供使用，生命很少形成 N-S 键，而且已经独立进化出了形成 N-S 键的能力，这表明生命对 N-S 化学的限制不在于其合成。我们提出了一个假设来解释生命对 N-S 键的使用极其有限的原因：N-S 键化学与生物化学的基本部分，特别是与硫醇不相容。我们通过以下两种方法支持我们的假设：（1）对含 N-S 键的天然产物的出现进行定量分析；（2）选定的 N-S 化合物与关键生物分子之间的反应性实验。这项工作提供了一个例子，说明了为什么生命几乎排除了一个独特的化学空间区域。结合未来的例子，这个潜在的新研究领域可能会为生命通过化学空间及其起源和早期进化提供新的见解。
