A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet

Mayer-Bacon, Christopher; Meringer, Markus; Havel, Riley; Aponte, José C.; Freeland, Stephen J.

doi:10.1007/s00239-022-10061-5

Cited by 4 publications

(9 citation statements)

References 53 publications

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“…In other words, organic chemistry offers good reasons why any life might be expected to "encounter" amino acids (Figure 8: outer shell), chemistry provides good reasoning why it might use them and biology shows us how resilient and versatile would be the result. in both depth [144,222] and breadth [230], and has even detected strong, non-random patterns in additional amino acid properties [180,191]. The most recent expansion of this work has now identified for the first time specific examples of entirely xeno amino acids that match the statistical profile established by life since LUCA [175].…”

Section: Would Xeno Biochemistry Use Amino Acids?mentioning

confidence: 82%

“…The two specific physicochemical properties involved (volume and hydrophobicity) are known to guide protein folding [228,229]. Subsequent work has expanded this evidence in both depth [144,222] and breadth [230], and has even detected strong, non-random patterns in additional amino acid properties [180,191]. The most recent expansion of this work has now identified for the first time specific examples of entirely xeno amino acids that match the statistical profile established by life since LUCA [175].…”

Section: Clues From Molecular Evolutionary Biology: Natural Selection...mentioning

confidence: 90%

“…Like amino acid backbones, many side chains are possible beyond the 20 found within the standard genetic code. (A) Abiotic synthesis: various other side chains are found in meteorites and produced by prebiotic simulations (see [144]: supplementary data); (B) biological: many other side chains are used by living organisms (see [145]); (C) synthetic biology has successfully incorporated hundreds of alternative side chains into protein synthesis, including numerous far larger than anything found within the standard genetic code, shown as red diamonds [146][147][148] (also see [138]). (D) Theoretical: the addition of each carbon atom increases exponentially (combinatorially) the number of chemical structures that are possible (see: [41]).…”

Section: Would a Xeno Biochemistry Use Different Side-chains?mentioning

confidence: 99%

“…It is then the emerging, new synthesis of these three subfields which promises exciting new progress. [10,18,52,60,78,131,132,144,147,161, converging on direct exploration of alternative amino acid alphabets, traced back through diverse subdisciplines to foundational works. This literature involves both theory and experiment.…”

Section: Would a Xeno Biochemistry Use Different Side-chains?mentioning

confidence: 99%

“…De novo protein design builds from Anfinsen's [174] demonstration that a protein's three-dimensional structure is produced by the specific sequence of amino acid side [10,18,52,60,78,131,132,144,147,161, converging on direct exploration of alternative amino acid alphabets, traced back through diverse subdisciplines to foundational works. This literature involves both theory and experiment.…”

Section: Clues From De Novo Protein Design: Altering the Functional U...mentioning

confidence: 99%

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Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It

Brown,

Mayer-Bacon,

Freeland

2023

Life

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Would another origin of life resemble Earth’s biochemical use of amino acids? Here, we review current knowledge at three levels: (1) Could other classes of chemical structure serve as building blocks for biopolymer structure and catalysis? Amino acids now seem both readily available to, and a plausible chemical attractor for, life as we do not know it. 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. However, assertions that other backbones are physicochemically impossible have relaxed into arguments that they are disadvantageous. (3) Would we expect a similar set of side chains to those within the genetic code? Many plausible alternatives exist. Furthermore, evidence exists for both evolutionary advantage and physicochemical constraint as explanatory factors for those encoded by life. Overall, as focus shifts from amino acids as a chemical class to specific side chains used by post-LUCA biology, 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) expanding evidence about amino acids as attractors within chemical evolution; (b) extending characterization of other backbones relative to biological proteins; and (c) merging computing and laboratory explorations of structures and functions unlocked by xeno peptides.

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Section: Would Xeno Biochemistry Use Amino Acids?mentioning

confidence: 82%

Section: Clues From Molecular Evolutionary Biology: Natural Selection...mentioning

confidence: 90%

Section: Would a Xeno Biochemistry Use Different Side-chains?mentioning

confidence: 99%

Section: Would a Xeno Biochemistry Use Different Side-chains?mentioning

confidence: 99%

Section: Clues From De Novo Protein Design: Altering the Functional U...mentioning

confidence: 99%

See 3 more Smart Citations

Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It

Brown,

Mayer-Bacon,

Freeland

2023

Life

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What Would an Alien Amino Acid Alphabet Look Like and Why?

2023

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Origins of Life: Chemistry and Evolution

Matange,

Rajaei,

Schuster

et al. 2023

Preprint

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Progress in understanding the origins of life will be enhanced if models and their predictions are clearly understood and explicitly articulated. Two distinct models can be used to explain the genesis of biopolymers during the origins of life. In one model, which has been pursued for nearly 50 years, RNA is the result of inherent chemical reactivities of prebiotic chemical species. RNA invented evolution. This model enables the prediction that if the conditions of the ancient earth are sufficiently constrained, chemists will discover the direct synthetic pathways that produced RNA. In a fundamentally different model, which is more recent, RNA and other biopolymers are proposed to be the result of prolonged, creative, selection-based changes that occurred during chemical evolution and overlap with early biological evolution. Evolution invented RNA. In this evolutionary model, inherent chemical reactivities are not necessarily relevant to the origins of life and do not predict biosynthesis. These two models are fundamentally different from one another and guide design of very different experimental approaches to test their underlying assumptions. It is currently undetermined which model, or a hybrid of them, is closer to reality.

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A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet

Cited by 4 publications

References 53 publications

Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It

Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It

What Would an Alien Amino Acid Alphabet Look Like and Why?

Origins of Life: Chemistry and Evolution

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