scholarly journals The number of active metabolic pathways is bounded by the number of cellular constraints at maximal metabolic rates

2017 ◽  
Author(s):  
Daan H. de Groot ◽  
Coco van Boxtel ◽  
Robert Planqué ◽  
Frank J. Bruggeman ◽  
Bas Teusink

AbstractGrowth rate is a near-universal selective pressure across microbial species. High growth rates require hundreds of metabolic enzymes, each with different nonlinear kinetics, to be precisely tuned within the bounds set by physicochemical constraints. Yet, the metabolic behaviour of many species is characterized by simple relations between growth rate, enzyme expression levels and metabolic rates. We asked if this simplicity could be the outcome of optimisation by evolution. Indeed, when the growth rate is maximized –in a static environment under mass-conservation and enzyme expression constraints– we prove mathematically that the resulting optimal metabolic flux distribution is described by a limited number of subnetworks, known as Elementary Flux Modes (EFMs). We show that, because EFMs are the minimal subnetworks leading to growth, a small active number automatically leads to the simple relations that are measured. We find that the maximal number of flux-carrying EFMs is determined only by the number of imposed constraints on enzyme expression, not by the size, kinetics or topology of the network. This minimal-EFM extremum principle is illustrated in a graphical framework, which explains qualitative changes in microbial behaviours, such as overflow metabolism and co-consumption, and provides a method for identification of the enzyme expression constraints that limit growth under the prevalent conditions. The extremum principle applies to all microorganisms that are selected for maximal growth rates under protein concentration constraints, for example the solvent capacities of cytosol, membrane or periplasmic space.Author summaryThe microbial genome encodes for a large network of enzyme-catalyzed reactions. The reaction rates depend on concentrations of enzymes and metabolites, which in turn depend on those rates. Cells face a number of biophysical constraints on enzyme expression, for example due to a limited membrane area or cytosolic volume. Considering this complexity and nonlinearity of metabolism, how is it possible, that experimental data can often be described by simple linear models? We show that it is evolution itself that selects for simplicity. When reproductive rate is maximised, the number of active independent metabolic pathways is bounded by the number of growth-limiting enzyme constraints, which is typically small. A small number of pathways automatically generates the measured simple relations. We identify the importance of growth-limiting constraints in shaping microbial behaviour, by focussing on their mechanistic nature. We demonstrate that overflow metabolism – an important phenomenon in bacteria, yeasts, and cancer cells – is caused by two constraints on enzyme expression. We derive experimental guidelines for constraint identification in microorganisms. Knowing these constraints leads to increased understanding of metabolism, and thereby to better predictions and more effective manipulations.

2017 ◽  
Author(s):  
Meike T. Wortel ◽  
Elad Noor ◽  
Michael Ferris ◽  
Frank J. Bruggeman ◽  
Wolfram Liebermeister

AbstractMicrobes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism inE. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts.Author SummaryWhen cells compete for nutrients, those that grow faster and produce more offspring per time are favored by natural selection. In contrast, when cells need to maximize the cell number at a limited nutrient supply, fast growth does not matter and an efficient use of nutrients (i.e. high biomass yield) is essential. This raises a basic question about metabolism: can cells achieve high growth rates and yields simultaneously, or is there a conflict between the two goals? Using a new modeling method called Enzymatic Flux Cost Minimization (EFCM), we predict cellular growth rates and find that growth rate/yield trade-offs and the ensuing preference for enzyme-efficient or substrate-efficient metabolic pathways are not universal, but depend on growth conditions such as external glucose and oxygen concentrations.


Paleobiology ◽  
2012 ◽  
Vol 38 (2) ◽  
pp. 335-349 ◽  
Author(s):  
Jorge Cubo ◽  
Nathalie Le Roy ◽  
Cayetana Martinez-Maza ◽  
Laetitia Montes

The clade Archosauria contains two very different sister groups in terms of diversity (number of species) and disparity (phenotypic variation): Crurotarsi (taxa more closely related to crocodiles than to birds) and Ornithodira (pterosaurs and dinosaurs including birds). The extant species of Crurotarsi may constitute a biased sample of past biodiversity regarding growth patterns and metabolic rates. Bone histological characters can be conserved over hundreds of millions of years in the fossil record and potentially contain information about individual age at death, age at sexual maturity, bone growth rates, and basal metabolic rates of extinct vertebrates. Using a sample of extant amniotes, we have constructed a paleobiological model to estimate bone growth rate from bone histological traits. Cross-validation tests show that this model is reliable. We then used it to estimate bone growth rates in a sample of extinct archosaurs including Crurotarsi and Ornithodira. After testing for phylogenetic signal, optimization of femoral growth rates through squared change parsimony onto a time-calibrated tree of amniotes shows two divergent evolutionary trends: whereas bone growth rates increase from the last common ancestor of Ornithodira to extant birds, they decrease from the last common ancestor of Crurotarsi to extant crocodiles. However, we conclude, on the basis of recent evidence for unidirectional airflow in the lungs of alligators, that crocodiles may have retained the capacity of growing at high rates.


1996 ◽  
Vol 26 (9) ◽  
pp. 1569-1576 ◽  
Author(s):  
R.S. Criddle ◽  
T.S. Anekonda ◽  
R.M. Sachs ◽  
R.W. Breidenbach ◽  
L.D. Hansen

This paper examines the relation between respiratory physiology and growth rate and the effects of environment on this relation for the purpose of developing means for accelerating and improving selection of trees for biomass production. The relations among biomass production, respiratory metabolism, and growth temperature in controlled environments were determined for three Eucalyptus genotypes (clones). Eucalyptuscamaldulensis 4016, E. camaldulensis C11, and Eucalyptusgundal (Eucalyptusgunnii × Eucalyptusdalrympleana hybrid) GD1 were selected for this study because of known qualitative differences in their field growth responses to temperature. These clones were grown in controlled environments at three temperatures. Measurements were made of growth rate, metabolic heat rate, and dark CO2 production rate for plants grown at each of the three temperatures. This allowed determination of respiration rates of plants originally adapted for growth in different climates, but acclimated during growth at three different controlled temperatures, and also determination of respiration changes resulting from short-term changes in temperature. Growth rates of the three clones differed in their patterns of response to changes in growth temperature. For example, C11 grew most rapidly at the highest temperature, while GD1 was slowest at high temperature. Metabolic rates and the temperature dependence of metabolic rates of the clones differed and the pattern of differences changed when plants became acclimated to growth at different temperatures. Changes in metabolic properties of the three clones with growth and measurement temperatures are consistent with the growth rate changes. In general, increased growth rate was accompanied by increased respiration rate measured either as heat rate or as rate of CO2 production. Growth rates were inversely related to two measures of metabolic energy use efficiency. Growth rates decreased as values of heat loss per gram dry weight produced and values of heat loss per mole of CO2 produced increased. Recognition of these relations between growth rate and respiration parameters at different temperatures in controlled environement may allow prediction of relative growth rate performance of Eucalyptus clones over a range of growth climates.


1990 ◽  
Vol 55 (7) ◽  
pp. 1691-1707 ◽  
Author(s):  
Miloslav Karel ◽  
Jiří Hostomský ◽  
Jaroslav Nývlt ◽  
Axel König

Crystal growth rates of copper sulphate pentahydrate (CuSO4.5 H2O) determined by different authors and methods are compared. The methods included in this comparison are: (i) Measurement on a fixed crystal suspended in a streaming solution, (ii) measurement on a rotating disc, (iii) measurement in a fluidized bed, (iv) measurement in an agitated suspension. The comparison involves critical estimation of the supersaturation used in measurements, of shape factors used for data treatment and a correction for the effect of temperature. Conclusions are drawn for the choice of values to be specified when data of crystal growth rate measurements are published.


1989 ◽  
Vol 54 (11) ◽  
pp. 2951-2961 ◽  
Author(s):  
Miloslav Karel ◽  
Jaroslav Nývlt

Measured growth and dissolution rates of single crystals and tablets were used to calculate the overall linear rates of growth and dissolution of CuSO4.5 H2O crystals. The growth rate for the tablet is by 20% higher than that calculated for the single crystal. It has been concluded that this difference is due to a preferred orientation of crystal faces on the tablet surface. Calculated diffusion coefficients and thicknesses of the diffusion and hydrodynamic layers in the vicinity of the growing or dissolving crystal are in good agreement with published values.


2021 ◽  
pp. 0272989X2110222
Author(s):  
Yuwen Gu ◽  
Elise DeDoncker ◽  
Richard VanEnk ◽  
Rajib Paul ◽  
Susan Peters ◽  
...  

It is long perceived that the more data collection, the more knowledge emerges about the real disease progression. During emergencies like the H1N1 and the severe acute respiratory syndrome coronavirus 2 pandemics, public health surveillance requested increased testing to address the exacerbated demand. However, it is currently unknown how accurately surveillance portrays disease progression through incidence and confirmed case trends. State surveillance, unlike commercial testing, can process specimens based on the upcoming demand (e.g., with testing restrictions). Hence, proper assessment of accuracy may lead to improvements for a robust infrastructure. Using the H1N1 pandemic experience, we developed a simulation that models the true unobserved influenza incidence trend in the State of Michigan, as well as trends observed at different data collection points of the surveillance system. We calculated the growth rate, or speed at which each trend increases during the pandemic growth phase, and we performed statistical experiments to assess the biases (or differences) between growth rates of unobserved and observed trends. We highlight the following results: 1) emergency-driven high-risk perception increases reporting, which leads to reduction of biases in the growth rates; 2) the best predicted growth rates are those estimated from the trend of specimens submitted to the surveillance point that receives reports from a variety of health care providers; and 3) under several criteria to queue specimens for viral subtyping with limited capacity, the best-performing criterion was to queue first-come, first-serve restricted to specimens with higher hospitalization risk. Under this criterion, the lab released capacity to subtype specimens for each day in the trend, which reduced the growth rate bias the most compared to other queuing criteria. Future research should investigate additional restrictions to the queue.


Geosciences ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 187
Author(s):  
Rolf Vieten ◽  
Francisco Hernandez

Speleothems are one of the few archives which allow us to reconstruct the terrestrial paleoclimate and help us to understand the important climate dynamics in inhabited regions of our planet. Their time of growth can be precisely dated by radiometric techniques, but unfortunately seasonal radiometric dating resolution is so far not feasible. Numerous cave environmental monitoring studies show evidence for significant seasonal variations in parameters influencing carbonate deposition (calcium-ion concentration, cave air pCO2, drip rate and temperature). Variations in speleothem deposition rates need to be known in order to correctly decipher the climate signal stored in the speleothem archive. StalGrowth is the first software to quantify growth rates based on cave monitoring results, detect growth seasonality and estimate the seasonal growth bias. It quickly plots the predicted speleothem growth rate together with the influencing cave environmental parameters to identify which parameter(s) cause changes in speleothem growth rate, and it can also identify periods of no growth. This new program has been applied to multiannual cave monitoring studies in Austria, Gibraltar, Puerto Rico and Texas, and it has identified two cases of seasonal varying speleothem growth.


Plants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 31 ◽  
Author(s):  
Maria N. Metsoviti ◽  
George Papapolymerou ◽  
Ioannis T. Karapanagiotidis ◽  
Nikolaos Katsoulas

In this research, the effect of solar irradiance on Chlorella vulgaris cultivated in open bioreactors under greenhouse conditions was investigated, as well as of ratio of light intensity in the 420–520 nm range to light in the 580–680 nm range (I420–520/I580–680) and of artificial irradiation provided by red and white LED lamps in a closed flat plate laboratory bioreactor on the growth rate and composition. The increase in solar irradiance led to faster growth rates (μexp) of C. vulgaris under both environmental conditions studied in the greenhouse (in June up to 0.33 d−1 and in September up to 0.29 d−1) and higher lipid content in microalgal biomass (in June up to 25.6% and in September up to 24.7%). In the experiments conducted in the closed bioreactor, as the ratio I420–520/I580–680 increased, the specific growth rate and the biomass, protein and lipid productivities increased as well. Additionally, the increase in light intensity with red and white LED lamps resulted in faster growth rates (the μexp increased up to 0.36 d−1) and higher lipid content (up to 22.2%), while the protein, fiber, ash and moisture content remained relatively constant. Overall, the trend in biomass, lipid, and protein productivities as a function of light intensity was similar in the two systems (greenhouse and bioreactor).


1974 ◽  
Vol 11 (03) ◽  
pp. 437-444 ◽  
Author(s):  
Benoit Mandelbrot

Luria and Delbrück (1943) have observed that, in old cultures of bacteria that have mutated at random, the distribution of the number of mutants is extremely long-tailed. In this note, this distribution will be derived (for the first time) exactly and explicitly. The rates of mutation will be allowed to be either positive or infinitesimal, and the rate of growth for mutants will be allowed to be either equal, greater or smaller than for non-mutants. Under the realistic limit condition of a very low mutation rate, the number of mutants is shown to be a stable-Lévy (sometimes called “Pareto Lévy”) random variable, of maximum skewness ß, whose exponent α is essentially the ratio of the growth rates of non-mutants and of mutants. Thus, the probability of the number of mutants exceeding the very large value m is proportional to m –α–1 (a behavior sometimes referred to as “asymptotically Paretian” or “hyperbolic”). The unequal growth rate cases α ≠ 1 are solved for the first time. In the α = 1 case, a result of Lea and Coulson is rederived, interpreted, and generalized. Various paradoxes involving divergent moments that were encountered in earlier approaches are either absent or fully explainable. The mathematical techniques used being standard, they will not be described in detail, so this note will be primarily a collection of results. However, the justification for deriving them lies in their use in biology, and the mathematically unexperienced biologists may be unfamiliar with the tools used. They may wish for more details of calculations, more explanations and Figures. To satisfy their needs, a report available from the author upon request has been prepared. It will be referred to as Part II.


1978 ◽  
Vol 14 (1) ◽  
pp. 1-5 ◽  
Author(s):  
J. L. Monteith

SUMMARYFigures for maximum crop growth rates, reviewed by Gifford (1974), suggest that the productivity of C3 and C4 species is almost indistinguishable. However, close inspection of these figures at source and correspondence with several authors revealed a number of errors. When all unreliable figures were discarded, the maximum growth rate for C3 stands fell in the range 34–39 g m−2 d−1 compared with 50–54 g m−2 d−1 for C4 stands. Maximum growth rates averaged over the whole growing season showed a similar difference: 13 g m−2 d−1 for C3 and 22 g m−2 d−1 for C4. These figures correspond to photosynthetic efficiencies of approximately 1·4 and 2·0%.


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