The Canonical Network of Autotrophic Intermediary Metabolism: Minimal Metabolome of a Reductive Chemoautotroph

Srinivasan, Vijayasarathy; Morowitz, Harold J.

doi:10.1086/bblv216n2p126

Cited by 37 publications

(33 citation statements)

References 13 publications

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“…2 and Scheme 1 pathway "H") in addition to urea, carbodiimide and various carboxylic acids, three of which (succinic, maleic and fumaric acids) are intermediates of the reductive version of the citric acid cycle (rTCA) (see Section 3). This cycle of autocatalytic processes is probably the most ancient anabolic core in intermediary metabolism [90,91]. Carbodiimide, a product of urea dehydration, is a well-known condensing agent able to catalyze the formation of the peptide and phosphoester bonds in proteins and oligonucleotides, respectively [92].…”

Section: Syntheses Of Nucleic Bases From Formamidementioning

confidence: 99%

“…Whether autocatalytic cycles have been able to establish themselves is matter of open debate [8,16,17,21,90,133,134]. In particular, the onset of metabolic cycles on the prebiotic Earth has been dubbed as implausible [134], mostly on the basis of kinetic considerations and on the difficulty of justifying both thermodynamically and kinetically the exclusion of side reactions that would disrupt the cycle.…”

Section: Synthesis Of Pre-metabolic Componentsmentioning

confidence: 99%

“…This opinion is not generally shared [8,12,14,16,17,21,[84][85][86]132,134,135]. The similarity of spontaneous cycles with metabolic ones has been established for the formose reaction [136][137][138], which converts formaldehyde to various sugars and other products, and has been suggested for the triose-ammonia reaction [139] and for the acceleration of the HCN oligomerization [140].…”

Section: Synthesis Of Pre-metabolic Componentsmentioning

confidence: 99%

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Formamide and the origin of life

Saladino

Crestini

Pino

et al. 2012

Physics of Life Reviews

261

234

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The complexity of life boils down to the definition: "self-sustained chemical system capable of undergoing Darwinian evolution" (Joyce, 1994) [1]. The term "self-sustained" implies a set of chemical reactions capable of harnessing energy from the environment, using it to carry out programmed anabolic and catabolic functions. We briefly present our opinion on the general validity of this definition.Running anabolic and catabolic functions entails complex chemical information whose stability, reproducibility and evolution constitute the core of what is dubbed genetics.Life as-we-know-it is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, carbon). Other elements like phosphorus and sulphur play important but ancillary and potentially replaceable roles.The reproducible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information that we consider living entities. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, were embedded in physical-chemical conditions favourable for the onset of both.The most abundant three-atoms organic compound in interstellar environment is hydrogen cyanide HCN, the most abundant three-atoms inorganic compound is water H 2 O. The combination of the two results in the formation of formamide H 2 NCOH. We have explored the chemistry of formamide in conditions compatible with the synthesis and the stability of compounds of potential pre-genetic and pre-metabolic interest. We discuss evidence showing (i) that all the compounds necessary for the build-up of nucleic acids are easily obtained abiotically, (ii) that essentially all the steps leading to the spontaneous generation of RNA are abiotically possible, (iii) that the key compounds of extant metabolic cycles are obtained in the same chemical frame, often in the same test tube.How close are these observations to a plausible scenario for the origin of life?

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Section: Syntheses Of Nucleic Bases From Formamidementioning

confidence: 99%

Section: Synthesis Of Pre-metabolic Componentsmentioning

confidence: 99%

Section: Synthesis Of Pre-metabolic Componentsmentioning

confidence: 99%

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Formamide and the origin of life

Saladino

Crestini

Pino

et al. 2012

Physics of Life Reviews

261

234

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“…We can argue for the existence of a universal anabolic, autotrophic network [50,51] that comprises the chemistry essential to life. We can then separate the structural requirements and evolutionary history of the universal network from secondary complexities, which we will argue originate in the diversification of species and the concurrent processes of assembly of ecological communities.…”

Section: Hierarchy In Metabolism and The Role Of Individuals And Ecomentioning

confidence: 99%

The compositional and evolutionary logic of metabolism

2012

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Metabolism is built on a foundation of organic chemistry, and employs structures and interactions at many scales. Despite these sources of complexity, metabolism also displays striking and robust regularities in the forms of modularity and hierarchy, which may be described compactly in terms of relatively few principles of composition. These regularities render metabolic architecture comprehensible as a system, and also suggests the order in which layers of that system came into existence. In addition metabolism also serves as a foundational layer in other hierarchies, up to at least the levels of cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, motivates us to interpret metabolism as a source of causation or constraint on many forms of organization in the biosphere. Many of the forms of modularity and hierarchy exhibited by metabolism are readily interpreted as stages in the emergence of catalytic control by living systems over organic chemistry, sometimes recapitulating or incorporating geochemical mechanisms. We identify as modules, either subsets of chemicals and reactions, or subsets of functions, that are re-used in many contexts with a conserved internal structure. At the small molecule substrate level, module boundaries are often associated with the most complex reaction mechanisms, catalyzed by highly conserved enzymes. Cofactors form a biosynthetically and functionally distinctive control layer over the small-molecule substrate. The most complex members among the cofactors are often associated with the reactions at module boundaries in the substrate networks, while simpler cofactors participate in widely generalized reactions. The highly tuned chemical structures of cofactors (sometimes exploiting distinctive properties of the elements of the periodic table) thereby act as 'keys' that incorporate classes of organic reactions within biochemistry. Module boundaries provide the interfaces where change is concentrated, when we catalogue extant diversity of metabolic phenotypes. The same modules that organize the compositional diversity of metabolism are argued, with many explicit examples, to have governed long-term evolution. Early evolution of core metabolism, and especially of carbon-fixation, appears to have required very few innovations, and to have used few rules of composition of conserved modules, to produce adaptations to simple chemical or energetic differences of environment without diverse solutions and without historical contingency. We demonstrate these features of metabolism at each of several levels of hierarchy, beginning with the small-molecule metabolic substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Content from this work may be used under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 licence.

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“…A minimal metabolic network of 50 enzymatic reactions was derived from the theoretically inferred minimal gene set of Gil et al (25); it was shown that the encoded metabolism was consistent and that the network's topological parameters were similar to those of natural metabolic networks (46). Another work performed data mining on the KEGG Pathways database in an effort to obtain a minimal anabolic network and the correspondent minimal metabolome for a reductive chemoautotroph (47). The resulting metabolic network comprised 287 metabolites, with more than half being intermediates in the biosynthesis of monomers.…”

Section: Other Minimal Sets Of Componentsmentioning

confidence: 99%

Systems Biology Perspectives on Minimal and Simpler Cells

Xavier

Patil

Rocha

2014

Microbiol Mol Biol Rev

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SUMMARY The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells.

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The Canonical Network of Autotrophic Intermediary Metabolism: Minimal Metabolome of a Reductive Chemoautotroph

Cited by 37 publications

References 13 publications

Formamide and the origin of life

Formamide and the origin of life

The compositional and evolutionary logic of metabolism

Systems Biology Perspectives on Minimal and Simpler Cells

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