Metal Catalysts and the Origin of Life

Belmonte, Luca; Mansy, Sheref S.

doi:10.2113/gselements.12.6.413

Cited by 44 publications

(43 citation statements)

References 26 publications

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“…The Earth is rich in metal ions, so biology has evolved in a way that exploits this abundant resource. [39,40] For example, Mg 2+ plays structural and catalytic roles necessary for the activity of extant nucleic acids, proteins, and small molecules. Although there are places with low concentrations of metal ions, [31,32] even bodies of fresh water would experience transiently high concentrations of salt during the types of wet-dry cycles frequently invoked to aid the dehydration reactions needed for the synthesis of biological polymers.…”

Section: Resultsmentioning

confidence: 99%

Cyclophospholipids Increase Protocellular Stability to Metal Ions

Toparlak¹,

Karki²,

Ortuno³

et al. 2019

Preprint

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<p>Model protocells have long been constructed with fatty acids, because these lipids are prebiotically plausible and can, at least theoretically, support a protocell life cycle. However, fatty acid protocells are stable only within a narrow range of pH and metal ion concentration. This instability is particularly problematic as the early Earth would have had a range of conditions, and life as we know it is completely reliant on metal ions for catalysis and the folding and activity of biological polymers. Here we show that prebiotically plausible monoacyl cyclophospholipids form robust vesicles that survive a broad range of pH and high concentrations of Mg2+, Ca2+, and Na+. Importantly, stability to Mg2+ and Ca2+ is improved by the presence of environmental concentrations of Na+. These results suggest that cyclophospholipids, or lipids with similar characteristics, may have played a central role during the emergence of Darwinian evolution.</p>

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Section: Resultsmentioning

confidence: 99%

Cyclophospholipids Increase Protocellular Stability to Metal Ions

Toparlak¹,

Karki²,

Ortuno³

et al. 2019

Preprint

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“…Finding prebiotically relevant compounds with catalytic potential on biochemical reactions is one of the big challenges for understanding the origin of metabolism. To date, much of these prebiotically relevant catalytic activities have been ascribed to minerals and metals, while small (bio-)molecules, including amino acids, form only a tiny fraction of it (30,(49)(50)(51)(52). Yet, often the prebiotic reactions and pathways described do not map to the structure of extant metabolic networks.…”

Section: Discussionmentioning

confidence: 99%

“…The amino acid ligand, in addition to acting as a surrogate of metal catalysis, might also act as a scaffold between the substrate and the metal. This could be regarded as a possibility for how a transition from simple metal-ligand catalyst to longer peptides based on metal centers could have taken place (49,59).…”

Section: Discussionmentioning

confidence: 99%

Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway

Piedrafita

Varma

Castro

et al. 2020

Preprint

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How metabolic pathways emerged in early evolution remains largely unknown. Recently discovered chemical networks driven by iron and sulfur resemble reaction sequences found within glycolysis, gluconeogenesis, the oxidative and reductive Krebs cycle, the Wood Ljungdahl as well as the S-adenosylmethionine pathways, components of the core cellular metabolic network. These findings suggest that the evolution of central metabolism was primed by environmental chemical reactions, implying that non-enzymatic reaction networks served as a “template” in the evolution of enzymatic activities. We speculated that the turning point for this transition would depend on the catalytic properties of the simplest structural components of proteins, single amino acids. Here, we systematically combine constituents of Fe(II)-driven non-enzymatic reactions resembling glycolysis and pentose phosphate pathway (PPP), with single proteinogenic amino acids. Multiple reaction rates are enhanced by amino acids. In particular, cysteine is able to replace (and/or complement) the metal ion Fe(II) in driving the non-enzymatic formation of the RNA-backbone metabolite ribose 5-phosphate from 6-phosphogluconate, a rate-limiting reaction of the oxidative PPP. In the presence of both Fe(II) and cysteine, a complex is formed, enabling the non-enzymatic reaction to proceed at a wide range of temperatures. At mundane temperatures, this ‘minimal enzyme-like complex’ achieves a much higher specificity in the formation of ribose 5-phosphate than the Fe(II)-driven reaction at high temperatures. Hence, simple amino acids can accelerate key steps within metal-promoted metabolism-like chemical networks. Our results imply a stepwise scenario, in which environmental chemical networks served as primers in the early evolution of the metabolic network structure.Significance StatementThe evolutionary roots of metabolic pathways are barely understood. Here we show results consistent with a stepwise scenario during the evolution of (enzymatic) metabolism, starting from non-enzymatic chemical networks. By systematic screening of metabolic-like reactivities in vitro, and using high-throughput analytical techniques, we identify an iron/cysteine complex to act as a ‘minimal enzymelike complex’, which consists of a metal ion, an amino acid, and a sugar phosphate ligand. Integrated in a metal-driven, non-enzymatic pentose phosphate pathway, it promotes the formation of the RNA-backbone precursor ribose 5-phosphate at ambient temperature.

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“…This dependence on metals is not surprising since extant metabolism is completely reliant on the activity of metalloproteins in which the metallocofactor itself is largely responsible for the catalysis. 129 The point of metabolism is generally not to produce specific molecules. For example, ATP alone does not drive a reaction better than any other molecule in the absence of coupling chemistry.…”

Section: Metabolismmentioning

confidence: 99%

Progress in synthesizing protocells

Toparlak

Mansy

2018

Exp Biol Med (Maywood)

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The traditional route to investigating biology by perturbing living systems or by individually purifying and characterizing component parts is giving way to more complex endeavors where chemists and physicists attempt to build cells from scratch. Parallel efforts are underway that either exploits extant biological parts or prebiotically plausible molecules. Both approaches help to reveal the underlying physical–chemical forces that give rise to cellular function and highlight the important role played by polymers in regulating biological chemical systems. Although the success in RNA and lipid chemistry has led to the reconstitution of specific facets of cellular life, our understanding of dynamic, dissipative networks is currently too incomplete to allow for the construction of a self-sustained, integrated protocell. However, the presence of shared chemistry points to a promising path forward. Impact statement Advances in the understanding of the biophysics of membranes, the nonenzymatic and enzymatic polymerization of RNA, and in the design of complex chemical reaction networks have led to a new, integrated way of viewing the shared chemistry needed to sustain life. Although a protocell capable of Darwinian evolution has yet to be built, the seemingly disparate pieces are beginning to fit together. At the very least, better cellular mimics are on the horizon that will likely teach us much about the physicochemical underpinnings of cellular life.

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Metal Catalysts and the Origin of Life

Cited by 44 publications

References 26 publications

Cyclophospholipids Increase Protocellular Stability to Metal Ions

Cyclophospholipids Increase Protocellular Stability to Metal Ions

Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway

Progress in synthesizing protocells

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