Publications by authors named "Avi I Flamholz"

Aerobes require dioxygen (O) to grow; anaerobes do not. However, nearly all microbes-aerobes, anaerobes, and facultative organisms alike-express enzymes whose substrates include O, if only for detoxification. This presents a challenge when trying to assess which organisms are aerobic from genomic data alone.

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Rubisco is the primary CO fixing enzyme of the biosphere yet has slow kinetics. The roles of evolution and chemical mechanism in constraining the sequence landscape of rubisco remain debated. In order to map sequence to function, we developed a massively parallel assay for rubisco using an engineered where enzyme function is coupled to growth.

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Microbial metabolism is impressively flexible, enabling growth even when available nutrients differ greatly from biomass in redox state. , for example, rearranges its physiology to grow on reduced and oxidized carbon sources through several forms of fermentation and respiration. To understand the limits on and evolutionary consequences of metabolic flexibility, we developed a mathematical model coupling redox chemistry with principles of cellular resource allocation.

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Our planet is a self-sustaining ecosystem powered by light energy from the sun, but roughly closed to matter. Many ecosystems on Earth are also approximately closed to matter and recycle nutrients by self-organizing stable nutrient cycles, e.g.

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Recent research has strengthened the notion that microbes allocate their biosynthetic capacity to maximize the growth rate, λ. Yet many microbes can grow substantially faster after laboratory evolution. Chure and Cremer advance a resource-allocation model, which they derive from first principles, that offers resolution to this conundrum.

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The history of Earth's carbon cycle reflects trends in atmospheric composition convolved with the evolution of photosynthesis. Fortunately, key parts of the carbon cycle have been recorded in the carbon isotope ratios of sedimentary rocks. The dominant model used to interpret this record as a proxy for ancient atmospheric CO is based on carbon isotope fractionations of modern photoautotrophs, and longstanding questions remain about how their evolution might have impacted the record.

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Gene regulation is central to cellular function. Yet, despite decades of work, we lack quantitative models that can predict how transcriptional control emerges from molecular interactions at the gene locus. Thermodynamic models of transcription, which assume that gene circuits operate at equilibrium, have previously been employed with considerable success in the context of bacterial systems.

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Cyanobacteria rely on CO-concentrating mechanisms (CCMs) to grow in today's atmosphere (0.04% CO). These complex physiological adaptations require ≈15 genes to produce two types of protein complexes: inorganic carbon (Ci) transporters and 100+ nm carboxysome compartments that encapsulate rubisco with a carbonic anhydrase (CA) enzyme.

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From a metabolic perspective, molecular oxygen (O) is arguably the most significant constituent of Earth's atmosphere. Nearly every facet of microbial physiology is sensitive to the presence and concentration of O, which is the most favorable terminal electron acceptor used by organisms and also a dangerously reactive oxidant. As O has such sweeping implications for physiology, researchers have developed diverse approaches to measure O concentrations in natural and laboratory settings.

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The Human Impacts Database (www.anthroponumbers.org) is a curated, searchable resource housing quantitative data relating to the diverse anthropogenic impacts on our planet, with topics ranging from sea-level rise to livestock populations, greenhouse gas emissions, fertilizer use, and beyond.

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Article Synopsis
  • Enzymes can be incredibly efficient catalysts, with some achieving "catalytic perfection" based on how quickly they can facilitate reactions.
  • Research indicates that not all enzyme superfamilies have the same catalytic properties; some may have developed through a "binding-first" approach, focusing on how they attach to substrates rather than on their catalytic abilities.
  • The concept of "uniform binding," proposed by Albery and Knowles, suggests that certain proto-catalysts can help direct reactions toward desired products without speeding them up, potentially explaining the evolution of some enzyme families that prioritize substrate binding over direct catalysis.
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SignificanceMetabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes [e.g.

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Making sense of the metabolism of microbial communities is a daunting task. Using denitrification as a model metabolism, a new paper shows that the rate of denitrification can often be predicted from genome contents, and dynamical models can be composed to predict denitrification rates of communities of two to five species.

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Article Synopsis
  • Wastewater surveillance of SARS-CoV-2 RNA can enhance COVID-19 response by correlating viral loads in wastewater with clinical case data, but challenges remain in accurately interpreting the data due to various external factors.
  • *The study analyzed SARS-CoV-2 concentrations in wastewater from multiple locations and found a strong detection rate linked to local COVID-19 case counts, particularly when rates exceeded 2.4 cases per 100,000 people.
  • *Normalization using crAssphage showed less variability and maintained a significant correlation with clinical data, but ultimately no method improved overall interpretation; the timing of wastewater sampling was crucial for aligning trends with clinical reporting.*
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Many photosynthetic organisms employ a CO concentrating mechanism (CCM) to increase the rate of CO fixation via the Calvin cycle. CCMs catalyze ≈50% of global photosynthesis, yet it remains unclear which genes and proteins are required to produce this complex adaptation. We describe the construction of a functional CCM in a non-native host, achieved by expressing genes from an autotrophic bacterium in an strain engineered to depend on rubisco carboxylation for growth.

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Carbon fixation via the Calvin cycle is constrained by the side activity of Rubisco with dioxygen, generating 2-phosphoglycolate. The metabolic recycling of phosphoglycolate was extensively studied in photoautotrophic organisms, including plants, algae, and cyanobacteria, where it is referred to as photorespiration. While receiving little attention so far, aerobic chemolithoautotrophic bacteria that operate the Calvin cycle independent of light must also recycle phosphoglycolate.

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Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus.

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Rubisco is the primary carboxylase of the Calvin cycle, the most abundant enzyme in the biosphere, and one of the best-characterized enzymes. On the basis of correlations between Rubisco kinetic parameters, it is widely posited that constraints embedded in the catalytic mechanism enforce trade-offs between CO specificity, , and maximum carboxylation rate, . However, the reasoning that established this view was based on data from ≈20 organisms.

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Background: The availability of microarrays measuring thousands of genes simultaneously across hundreds of biological conditions represents an opportunity to understand both individual biological pathways and the integrated workings of the cell. However, translating this amount of data into biological insight remains a daunting task. An important initial step in the analysis of microarray data is clustering of genes with similar behavior.

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