Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry

Abstract

A variety of organic chemicals were likely available on prebiotic Earth. These derived from diverse processes including atmospheric and geochemical synthesis and extraterrestrial input, and were delivered to environments including oceans, lakes, and subaerial hot springs. Prebiotic chemistry generates both molecules used by modern organisms, such as proteinaceous amino acids, as well as many molecule types not used in biochemistry. As prebiotic chemical diversity was likely high, and the core of biochemistry uses a rather small set of common building blocks, the majority of prebiotically available organic compounds may not have been those used in modern biochemistry. Chemical evolution was unlikely to have been able to discriminate which molecules would eventually be used in biology, and instead, interactions among compounds were governed simply by abundance and chemical reactivity. Previous work has shown that likely prebiotically available α-hydroxy acids can combinatorially polymerize into polyesters that self-assemble to create new phases which are able to compartmentalize other molecule types. The unexpectedly rich complexity of hydroxy acid chemistry and the likely enormous structural diversity of prebiotic organic chemistry suggests chemical evolution could have been heavily influenced by molecules not used in contemporary biochemistry, and that there is a considerable amount of prebiotic chemistry which remains unexplored.

Keywords: Origins of Life; Polyesters; non-biomolecules; prebiotic chemistry; protocells; wet-dry cycles.

Figure 1

Progressively zoomed in mass spectra (A–D) of Murchison meteorite soluble organic extracts, each focusing on a more narrow region within the previous spectrum, showing the diversity of meteoritic organics (and analyses). In (D), 11 molecular assignments were made in a narrow range of 0.012 Da, which suggests that even in such a narrow range, a large diversity of isomers may have existed in primitive chemical milieu. Reprinted with permission from Schmitt-Kopplin, Gabelica, Gougeon, Fekete, Kanawati, Harir, Gebefuegi, Eckel, and Hertkorn, 2010. “High molecular diversity of extraterrestrial organic matter in Murchison meteorite revealed 40 years after its fall.” Proc. Nat. Acad. Sci. USA. 107(7):12763-2768. [12] Copyright Schmitt-Kopplin, et al., with an exclusive License to Publish to NAS.

Figure 2

Mass spectrum of a complex product mixture from a laboratory simulation of an atmospheric discharge reaction consisting of liquid water, methane gas, and ammonium gas starting materials in the presence of cyanamide, showing the remarkable chemical diversity produced from a prebiotically plausible organic chemical reaction. Reprinted with permission from Parker, Cleaves, Bada, and Fernandez. “Quantitation of α-hydroxy acids in complex prebiotic mixtures via liquid chromatography/tandem mass spectrometry.” Rapid Commun. Mass Spectrom. 30(18):2043–2051. [23] Copyright John Wiley & Sons, Inc.

Figure 3

Mass spectra showing the synthesis of polyesters from simple drying of solutions of the alpha hydroxy acids (αHAs) (A) glycolic acid (GA), (B) lactic acid (LA), and (C) a mixture of five different αHAs (LA, GA, DL-2-hydroxy-4-methylpentanoic acid, DL-2-hydroxy-4-(methylsulfanyl) butanoic acid, and DL-3-phenyllactic acid). Insets show higher m/z regions. Asterisks represent peaks showing water loss. Reprinted with permission from Chandru, Guttenberg, Giri, Hongo, Butch, Mamajanov, and Cleaves. 2018. “Simple prebiotic synthesis of high diversity dynamic combinatorial polyester libraries.” Commun. Chem. 1:30. [38] under a Creative Commons License.

Scheme 1

Simple dehydration synthesis of an arbitrary number of αHAs with side-chains R₁ and R₂ (left), resulting in production of polyester polymers through condensation by loss of water molecules.

Figure 4

Rehydration of polyesters formed from wet–dry cycling of mixed αHA mixtures results in spontaneous assembly of microdroplets. LA = lactic acid, GA = glycolic acid, PA = phenyllactic acid, SA = 2-hydroxy-4-(methylsulfanyl)butanoic acid, MA = 2-hydroxy-4-methylpentanoic acid. Reprinted with permission from Jia, Chandru, Hongo, Afrin, Usui, Myojo, and Cleaves. 2019. “Membraneless polyester microdroplets as primordial compartments at the origins of life.” Proc. Nat. Acad. Sci. USA. 116(32):15830-15835. [40] Copyright Jia, T.Z., Chandru, K., et al., with an exclusive License to Publish to NAS.

Figure 5

Top: A prebiotic chemistry scenario in which a chemical, A, participates in a chemical reaction and produces a toxic byproduct, B, a molecule that inhibits reactions involving A. B accumulates and eventually results in the complete inhibition of reactions involving A (to produce B). Bottom: Chemical A in solution, coexisting with polyester droplets (blue). A produces the toxic molecule B as a byproduct. However, assuming A and B are sufficiently different chemically, B could preferentially partition into the droplets due to B’s affinity for that phase (due to polarity, electrostatic interactions, sterics, etc.), allowing A to continue reacting uninhibited by B. It should be stressed that this is but one possible scenario for the role such droplets could play in higher order prebiotic chemistry, one can easily enumerate numerous other, more complex systems, that could be explored experimentally.