Xeno Amino Acids: A look into biochemistry as we don’t know itOPEN ACCESS 

Sean M. Brown, Christopher Mayer-Bacon, Stephen Freeland

Preprint, to be submitted to Life


“Would another origin of life resemble Earth’s biochemistry? Here, consider that question specifically in terms of amino acids, reviewing current knowledge at three levels: 1) Could other chemical classes serve as building blocks for structure and catalysis? All indications at present are that amino acids are both readily available to, and a plausible chemical attractor for, life as we don’t know it. These are the same features that motivate current explorations for extraterrestrial life to “follow the water,” and amino acids thus remain important and tractable targets for astrobiological research 2) If amino acids are used, would we expect the same, L-alpha structural subclass used by life? Despite numerous ideas, it is not clear why life favors L-enantiomers. It seems clearer, however, why life on Earth uses the shortest possible (alpha) amino acid backbone, and why each carries only one side chain. Interestingly, assertions that other backbones are physicochemically impossible have relaxed into evidence that suggest L-α-amino acids are preferable. 3) Would we expect a similar set of side chains to those within the genetic code? Many plausible alternatives exist, along with evidence for both evolutionary advantage and physicochemical constraint. Overall, as focus shifts from amino acids as a chemical class to specific side chains used by post-LUCA life, the probable role of physicochemical constraint diminishes relative to that of biological evolution. Exciting opportunities now present themselves for laboratory work and computing to explore how changing the amino acid alphabet alters the universe of protein folds. Near-term milestones include: a) systemically generalizing evidence about amino acids as attractors within chemical evolution; b) extending characterization of other backbones relative to biological proteins; c) merging computing and laboratory explorations of structures/functions unlocked by xeno peptides.”