Essential plasticity and redundancy of metabolism unveiled by synthetic lethality analysis

We unravel how functional plasticity and redundancy are essential mechanisms underlying the ability to survive of metabolic networks. We perform an exhaustive computational screening of synthetic lethal reaction pairs in Escherichia coli in a minimal medium and we find that synthetic lethal pairs divide in two different groups depending on whether the synthetic lethal interaction works as a backup or as a parallel use mechanism, the first corresponding to essential plasticity and the second to essential redundancy. In E. coli, the analysis of pathways entanglement through essential redundancy supports the view that synthetic lethality affects preferentially a single function or pathway. In contrast, essential plasticity, the dominant class, tends to be inter-pathway but strongly localized and unveils Cell Envelope Biosynthesis as an essential backup for Membrane Lipid Metabolism. When comparing E. coli and Mycoplasma pneumoniae, we find that the metabolic networks of the two organisms exhibit a large difference in the relative importance of plasticity and redundancy which is consistent with the conjecture that plasticity is a sophisticated mechanism that requires a complex organization. Finally, coessential reaction pairs are explored in different environmental conditions to uncover the interplay between the two mechanisms. We find that synthetic lethal interactions and their classification in plasticity and redundancy are basically insensitive to medium composition, and are highly conserved even when the environment is enriched with nonessential compounds or overconstrained to decrease maximum biomass formation.Comment: 22 pages, 4 figure

Assessing the significance of knockout cascades in metabolic networks

Complex networks have been shown to be robust against random structural perturbations, but vulnerable against targeted attacks. Robustness analysis usually simulates the removal of individual or sets of nodes, followed by the assessment of the inflicted damage. For complex metabolic networks, it has been suggested that evolutionary pressure may favor robustness against reaction removal. However, the removal of a reaction and its impact on the network may as well be interpreted as selective regulation of pathway activities, suggesting a tradeoff between the efficiency of regulation and vulnerability. Here, we employ a cascading failure algorithm to simulate the removal of single and pairs of reactions from the metabolic networks of two organisms, and estimate the significance of the results using two different null models: degree preserving and mass-balanced randomization. Our analysis suggests that evolutionary pressure promotes larger cascades of non-viable reactions, and thus favors the ability of efficient metabolic regulation at the expense of robustness

El borat de zinc com a retardant de flama

Els borats són minerals que podem trobar a la natura i que contenen bor, el cinquè element de la taula periòdica. N'hi ha traces a roques, al sòl i a l'aigua. Tant el bor com el zinc són micronutrients essencials pel creixement de les plantes. Així mateix, les persones també els necessiten com a part important d'una dieta saludable i com un ingredient essencial en molts productes necessaris per tenir un estàndard de vida acceptable

Els plastòmers

Un plastòmer és un material polimèric que presenta propietats d'elastòmers termoplàstics, és a dir, presenta tant deformació plàstica com elastomèrica. Els plastòmers són una classe de copolímers que van sorgir amb els avenços en la polimerització amb catalitzadors metal·locènics i estan fabricats amb etilè i una alfa-olfina. Típicament, les alfa-olefines emprades són l'1-propè, l'1-butè, l'1-hexè i l'1-octè (el més fet servir actualment)

El carbonat de calci: molt més que un filler

El carbonat de calci és un dels compostos químics més emprats, més útils i més versàtils coneguts per l'home. La seva fórmula és CaCO3, té una aparença de pols blanca, no fa olor i és molt poc soluble en aigua i molt soluble en àcids. És la sal de calci més abundant a la naturalesa, a més d'ésser el component principal de les roques; representa el 15% dels sediments i de les roques sedimentàries de la Terra, i el 4% de l'escorça terrestre amb diferents formes i graus de puresa. Les plantes i els animals el necessiten per viure i poder formar els seus esquelets. L'ésser humà l'ha transformat en un producte bàsic en el seu desenvolupament industrial, mèdic, etc.; tant és així que gairebé tots els productes que ens envolten en la nostra vida quotidiana en contenen

Essential plasticity and redundancy of metabolism unveiled by synthetic lethality analysis

We unravel how functional plasticity and redundancy are essential mechanisms underlying the ability to survive of metabolic networks. We perform an exhaustive computational screening of synthetic lethal reaction pairs in Escherichia coli in a minimal medium and we find that synthetic lethal pairs divide in two different groups depending on whether the synthetic lethal interaction works as a backup or as a parallel use mechanism, the first corresponding to essential plasticity and the second to essential redundancy. In E. coli, the analysis of pathways entanglement through essential redundancy supports the view that synthetic lethality affects preferentially a single function or pathway. In contrast, essential plasticity, the dominant class, tends to be inter-pathway but strongly localized and unveils Cell Envelope Biosynthesis as an essential backup for Membrane Lipid Metabolism. When comparing E. coli and Mycoplasma pneumoniae, we find that the metabolic networks of the two organisms exhibit a large difference in the relative importance of plasticity and redundancy which is consistent with the conjecture that plasticity is a sophisticated mechanism that requires a complex organization. Finally, coessential reaction pairs are explored in different environmental conditions to uncover the interplay between the two mechanisms. We find that synthetic lethal interactions and their classification in plasticity and redundancy are basically insensitive to medium composition, and are highly conserved even when the environment is enriched with nonessential compounds or overconstrained to decrease maximum biomass formation

Predicting effects of structural stress in a genome-reduced model bacterial metabolism

Mycoplasma pneumoniae is a human pathogen recently proposed as a genome-reduced model for bacterial systems biology. Here, we study the response of its metabolic network to different forms of structural stress, including removal of individual and pairs of reactions and knockout of genes and clusters of co-expressed genes. Our results reveal a network architecture as robust as that of other model bacteria regarding multiple failures, although less robust against individual reaction inactivation. Interestingly, metabolite motifs associated to reactions can predict the propagation of inactivation cascades and damage amplification effects arising in double knockouts. We also detect a significant correlation between gene essentiality and damages produced by single gene knockouts, and find that genes controlling high-damage reactions tend to be expressed independently of each other, a functional switch mechanism that, simultaneously, acts as a genetic firewall to protect metabolism. Prediction of failure propagation is crucial for metabolic engineering or disease treatment