Coenzymes and Their Role in the Evolution of Life

Kirschning, Andreas

doi:10.1002/anie.201914786

Cited by 66 publications

(74 citation statements)

References 275 publications

(394 reference statements)

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“…Additionally, we do not discuss the biosynthesis of cofactors, whether organic or inorganic, 58,59 as this has been covered in a prebiotic context in a recent review. 60 Finally, we omit the geological context of "metabolism-first" theories of the origin of life, as this has been reviewed and speculated upon many times. [61][62][63]…”

Section: Introductionmentioning

confidence: 99%

Nonenzymatic Metabolic Reactions and Life’s Origins

2020

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Prebiotic chemistry aims to explain how the biochemistry of life as we know it came to be. Most efforts in this area have focused on provisioning compounds of importance to life by multi-step synthetic routes that do not resemble biochemistry. However, gaining insight into why core metabolism uses the molecules, reactions, pathways, and overall organization that it does requires us to consider molecules not only as synthetic end goals. Equally important are the dynamic processes that build them up and break them down. This perspective has led many researchers to the hypothesis that the first stage of the origin of life began with the onset of a primitive non-enzymatic version of metabolism, initially catalyzed by naturally occurring minerals and metal ions. This view of life's origins has come to be known as "metabolism first". Continuity with modern metabolism would require a primitive version of metabolism to build and break down ketoacids, sugars, amino acids, and ribonucleotides in much the same way as the pathways that do it today. This review discusses metabolic pathways of relevance to the origin of life in a manner accessible to chemists, and summarizes experiments suggesting several pathways might have their roots in prebiotic chemistry. Finally, key remaining milestones for the protometabolic hypothesis are highlighted.

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Section: Introductionmentioning

confidence: 99%

Nonenzymatic Metabolic Reactions and Life’s Origins

2020

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“…In fact, most universally conserved nucleotide cofactors are promiscuous, including NADH, FADH, acetyl CoA and ATP (42, 43, 45, 73). These promiscuous cofactors catalyse equivalent processes, such as the transfer of hydrogen, electrons, phosphate, acetyl or methyl groups (all fundamental features of metabolism), in many pathways across the entire metabolic network (3, 74, 75). Cofactors can catalyse these reactions without their enzymes (35-37), so the idea of an early era of biology when nucleotide monomers were the main catalysts has long held appeal (32, 33).…”

Section: Discussionmentioning

confidence: 99%

The limits of metabolic heredity in protocells

Palmeira

Colnaghi

Harrison

et al. 2022

Preprint

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The universal core of metabolism could have emerged from thermodynamically favoured prebiotic pathways at the origin of life. Starting with H2 and CO2, the synthesis of amino acids and mixed fatty acids, which self-assemble into protocells, is favoured under warm anoxic conditions. Here we address whether it is possible for protocells to evolve greater metabolic complexity, through positive feedbacks involving nucleotide catalysis. Using mathematical simulations to model metabolic heredity in protocells, based on branch points in proto-metabolic flux, we show that nucleotide catalysis can indeed promote protocell growth. This outcome only occurs when nucleotides directly catalyse CO2 fixation. Strong nucleotide catalysis of other pathways (e.g. fatty acids, amino acids) generally unbalances metabolism and slows down protocell growth, and when there is competition between catalytic functions cell growth collapses. Autocatalysis of nucleotide synthesis can promote growth but only if nucleotides also catalyse CO2 fixation; autocatalysis alone leads to the accumulation of nucleotides at the expense of CO2 fixation and protocell growth rate. Our findings offer a new framework for the emergence of greater metabolic complexity, in which nucleotides catalyse broad-spectrum processes such as CO2 fixation, hydrogenation and phosphorylation important to the emergence of genetic heredity at the origin of life.

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“…In addition to these observations from prebiotic chemistry and ribozyme research, evolutionary analysis of ancient protein families suggests that early protein enzymes likely used cofactors in general, as recently demonstrated for zinc-and molybdenum-specific metalloenzymes (Kacar et al 2017, Garcia et al 2020, and nucleotide-derived cofactors, specifically (Goldman et al 2013;Kirschning 2020). In one set of studies, Caetano-Anollés and colleagues chronologically ordered protein structures as defined by the SCOP database (Murzin et al 1995) from most ancient to most recent (Wang et al 2007;Caetano-Anollés et al 2009).…”

Section: Supporting Evidence and Future Directionsmentioning

confidence: 94%

Cofactors are Remnants of Life’s Origin and Early Evolution

Goldman

Kaçar

2021

J Mol Evol

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The RNA World is one of the most widely accepted hypotheses explaining the origin of the genetic system used by all organisms today. It proposes that the tripartite system of DNA, RNA, and proteins was preceded by one consisting solely of RNA, which both stored genetic information and performed the molecular functions encoded by that genetic information. Current research into a potential RNA World revolves around the catalytic properties of RNA-based enzymes, or ribozymes. Well before the discovery of ribozymes, Harold White proposed that evidence for a precursor RNA world could be found within modern proteins in the form of coenzymes, the majority of which contain nucleobases or nucleoside moieties, such as Coenzyme A and S-adenosyl methionine, or are themselves nucleotides, such as ATP and NADH (a dinucleotide). These coenzymes, White suggested, had been the catalytic active sites of ancient ribozymes, which transitioned to their current forms after the surrounding ribozyme scaffolds had been replaced by protein apoenzymes during the evolution of translation. Since its proposal four decades ago, this groundbreaking hypothesis has garnered support from several different research disciplines and motivated similar hypotheses about other classes of cofactors, most notably iron-sulfur cluster cofactors as remnants of the geochemical setting of the origin of life. Evidence from prebiotic geochemistry, ribozyme biochemistry, and evolutionary biology, increasingly supports these hypotheses. Certain coenzymes and cofactors may bridge modern biology with the past and can thus provide insights into the elusive and poorly-recorded period of the origin and early evolution of life.

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Coenzymes and Their Role in the Evolution of Life

Cited by 66 publications

References 275 publications

Nonenzymatic Metabolic Reactions and Life’s Origins

Nonenzymatic Metabolic Reactions and Life’s Origins

The limits of metabolic heredity in protocells

Cofactors are Remnants of Life’s Origin and Early Evolution

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