A quantitative description of light-limited cyanobacterial growth using flux balance analysis.

The metabolism of phototrophic cyanobacteria is an integral part of global biogeochemical cycles, and the capability of cyanobacteria to assimilate atmospheric CO2 into organic carbon has manifold potential applications for a sustainable biotechnology. To elucidate the properties of cyanobacterial metabolism and growth, computational reconstructions of genome-scale metabolic networks play an increasingly important role. Here, we present an updated reconstruction of the metabolic network of the cyanobacterium Synechocystis sp.

Trade-offs between the instantaneous growth rate and long-term fitness: Consequences for microbial physiology and predictive computational models.

Microbial systems biology has made enormous advances in relating microbial physiology to the underlying biochemistry and molecular biology. By meticulously studying model microorganisms, in particular Escherichia coli and Saccharomyces cerevisiae, increasingly comprehensive computational models predict metabolic fluxes, protein expression, and growth. The modeling rationale is that cells are constrained by a limited pool of resources that they allocate optimally to maximize fitness.

Characterizing isoprene production in cyanobacteria - Insights into the effects of light, temperature, and isoprene on Synechocystis sp. PCC 6803.

Engineering cyanobacteria for the production of isoprene and other terpenoids has gained increasing attention in the field of biotechnology. Several studies have addressed optimization of isoprene synthesis in cyanobacteria via enzyme and pathway engineering. However, only little attention has been paid to the optimization of cultivation conditions.

Time-Optimal Adaptation in Metabolic Network Models.

Analysis of metabolic models using constraint-based optimization has emerged as an important computational technique to elucidate and eventually predict cellular metabolism and growth. In this work, we introduce time-optimal adaptation (TOA), a new constraint-based modeling approach that allows us to evaluate the fastest possible adaptation to a pre-defined cellular state while fulfilling a given set of dynamic and static constraints. TOA falls into the mathematical problem class of time-optimal control problems, and, in its general form, can be broadly applied and thereby extends most existing constraint-based modeling frameworks.

Fast-growing phototrophic microorganisms and the productivity of phototrophic cultures.

Fast-growing cyanobacterial and microalgal strains are considered to be a promising resource to overcome current productivity barriers of phototrophic cultivation. The purpose of this communication, however, is to argue that a high maximal growth rate itself is not a sufficient or necessary property for high phototrophic productivity. Rather, the light-limited specific growth rate of a phototrophic microorganism is a product of several factors, including the rate of light absorption, the photosynthetic efficiency, and the maximal biomass yield per mol photons.

Deciphering the physiological response of Escherichia coli under high ATP demand.

One long-standing question in microbiology is how microbes buffer perturbations in energy metabolism. In this study, we systematically analyzed the impact of different levels of ATP demand in Escherichia coli under various conditions (aerobic and anaerobic, with and without cell growth). One key finding is that, under all conditions tested, the glucose uptake increases with rising ATP demand, but only to a critical level beyond which it drops markedly, even below wild-type levels.

Modelling microbial communities using biochemical resource allocation analysis.

To understand the functioning and dynamics of microbial communities is a fundamental challenge in current biology. To tackle this challenge, the construction of computational models of interacting microbes is an indispensable tool. There is, however, a large chasm between ecologically motivated descriptions of microbial growth used in many current ecosystems simulations, and detailed metabolic pathway and genome-based descriptions developed in the context of systems and synthetic biology.

Optimal proteome allocation strategies for phototrophic growth in a light-limited chemostat.

Background: Cyanobacteria and other phototrophic microorganisms allow to couple the light-driven assimilation of atmospheric [Formula: see text] directly to the synthesis of carbon-based products, and are therefore attractive platforms for microbial cell factories. While most current engineering efforts are performed using small-scale laboratory cultivation, the economic viability of phototrophic cultivation also crucially depends on photobioreactor design and culture parameters, such as the maximal areal and volumetric productivities. Based on recent insights into the cyanobacterial cell physiology and the resulting computational models of cyanobacterial growth, the aim of this study is to investigate the limits of cyanobacterial productivity in continuous culture with light as the limiting nutrient.

Quantitative insights into the cyanobacterial cell economy.

Phototrophic microorganisms are promising resources for green biotechnology. Compared to heterotrophic microorganisms, however, the cellular economy of phototrophic growth is still insufficiently understood. We provide a quantitative analysis of light-limited, light-saturated, and light-inhibited growth of the cyanobacterium sp.

Kinetic modeling of the Calvin cycle identifies flux control and stable metabolomes in Synechocystis carbon fixation.

Biological fixation of atmospheric CO2 via the Calvin-Benson-Bassham cycle has massive ecological impact and offers potential for industrial exploitation, either by improving carbon fixation in plants and autotrophic bacteria, or by installation into new hosts. A kinetic model of the Calvin-Benson-Bassham cycle embedded in the central carbon metabolism of the cyanobacterium Synechocystis sp. PCC 6803 was developed to investigate its stability and underlying control mechanisms.

The Circadian Clock Regulates Metabolic Phenotype Rewiring Via HKDC1 and Modulates Tumor Progression and Drug Response in Colorectal Cancer.

An endogenous molecular clockwork drives various cellular pathways including metabolism and the cell cycle. Its dysregulation is able to prompt pathological phenotypes including cancer. Besides dramatic metabolic alterations, cancer cells display severe changes in the clock phenotype with likely consequences in tumor progression and treatment response.

Modules of co-occurrence in the cyanobacterial pan-genome reveal functional associations between groups of ortholog genes.

Cyanobacteria are a monophyletic phylogenetic group of global importance and have received considerable attention as potential host organisms for the renewable synthesis of chemical bulk products from atmospheric CO2. The cyanobacterial phylum exhibits enormous metabolic diversity with respect to morphology, lifestyle and habitat. As yet, however, research has mostly focused on few model strains and cyanobacterial diversity is insufficiently understood.

A model of optimal protein allocation during phototrophic growth.

Photoautotrophic growth depends upon an optimal allocation of finite cellular resources to diverse intracellular processes. Commitment of a certain mass fraction of the proteome to a specific cellular function typically reduces the proteome available for other cellular functions. Here, we develop a semi-quantitative kinetic model of cyanobacterial phototrophic growth to describe such trade-offs of cellular protein allocation.

Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth.

Cyanobacteria are an integral part of Earth's biogeochemical cycles and a promising resource for the synthesis of renewable bioproducts from atmospheric CO Growth and metabolism of cyanobacteria are inherently tied to the diurnal rhythm of light availability. As yet, however, insight into the stoichiometric and energetic constraints of cyanobacterial diurnal growth is limited. Here, we develop a computational framework to investigate the optimal allocation of cellular resources during diurnal phototrophic growth using a genome-scale metabolic reconstruction of the cyanobacterium PCC 7942.

Activity and functional properties of the isocitrate lyase in the cyanobacterium Cyanothece sp. PCC 7424.

Cyanobacteria are ubiquitous photoautotrophs that assimilate atmospheric CO2 as their main source of carbon. Several cyanobacteria are known to be facultative heterotrophs that are able to grow on diverse carbon sources. For selected strains, assimilation of organic acids and mixotrophic growth on acetate has been reported for decades.

Maintaining the Gift of Life: Achieving Adherence in Adolescent Heart Transplant Recipients.

Since the beginning of United Network of Organ Sharing data collection in 1987, a total of 8,333 pediatric patients have received a heart transplant in the United States. Because these patients now have longer graft success with improved care and immunosuppression, many of them are entering adolescence and young adulthood. Primary care pediatric nurse practitioners need to be alert to the prevalence of noncompliance with treatment in heart transplant patients, which continues to be highest in adolescence.

Toward Multiscale Models of Cyanobacterial Growth: A Modular Approach.

Oxygenic photosynthesis dominates global primary productivity ever since its evolution more than three billion years ago. While many aspects of phototrophic growth are well understood, it remains a considerable challenge to elucidate the manifold dependencies and interconnections between the diverse cellular processes that together facilitate the synthesis of new cells. Phototrophic growth involves the coordinated action of several layers of cellular functioning, ranging from the photosynthetic light reactions and the electron transport chain, to carbon-concentrating mechanisms and the assimilation of inorganic carbon.

Feedback, Mass Conservation and Reaction Kinetics Impact the Robustness of Cellular Oscillations.

Oscillations occur in a wide variety of cellular processes, for example in calcium and p53 signaling responses, in metabolic pathways or within gene-regulatory networks, e.g. the circadian system.

A Comprehensively Curated Genome-Scale Two-Cell Model for the Heterocystous Cyanobacterium Anabaena sp. PCC 7120.

Anabaena sp. PCC 7120 is a nitrogen-fixing filamentous cyanobacterium. Under nitrogen-limiting conditions, a fraction of the vegetative cells in each filament terminally differentiate to nongrowing heterocysts.

Optimizing cyanobacterial product synthesis: Meeting the challenges.

The synthesis of renewable bioproducts using photosynthetic microorganisms holds great promise. Sustainable industrial applications, however, are still scarce and the true limits of phototrophic production remain unknown. One of the limitations of further progress is our insufficient understanding of the quantitative changes in photoautotrophic metabolism that occur during growth in dynamic environments.

A quantitative evaluation of ethylene production in the recombinant cyanobacterium Synechocystis sp. PCC 6803 harboring the ethylene-forming enzyme by membrane inlet mass spectrometry.

The prediction of the world's future energy consumption and global climate change makes it desirable to identify new technologies to replace or augment fossil fuels by environmentally sustainable alternatives. One appealing sustainable energy concept is harvesting solar energy via photosynthesis coupled to conversion of CO2 into chemical feedstock and fuel. In this work, the production of ethylene, the most widely used petrochemical produced exclusively from fossil fuels, in the model cyanobacterium Synechocystis sp.

Resource allocation in metabolic networks: kinetic optimization and approximations by FBA.

Based on recent theoretical results on optimal flux distributions in kinetic metabolic networks, we explore the congruences and differences between solutions of kinetic optimization problems and results obtained by constraint-based methods. We demonstrate that, for a certain resource allocation problem, kinetic optimization and standard flux balance analysis (FBA) give rise to qualitatively different results. Furthermore, we introduce a variant of FBA, called satFBA, whose predictions are in qualitative agreement with kinetic optimization.

Elucidating temporal resource allocation and diurnal dynamics in phototrophic metabolism using conditional FBA.

The computational analysis of phototrophic growth using constraint-based optimization requires to go beyond current time-invariant implementations of flux-balance analysis (FBA). Phototrophic organisms, such as cyanobacteria, rely on harvesting the sun's energy for the conversion of atmospheric CO2 into organic carbon, hence their metabolism follows a strongly diurnal lifestyle. We describe the growth of cyanobacteria in a periodic environment using a new method called conditional FBA.

An algorithm for the reduction of genome-scale metabolic network models to meaningful core models.

Background: Constraint-based analysis of genome-scale metabolic models has become a key methodology to gain insights into functions, capabilities, and properties of cellular metabolism. Since their inception, the size and complexity of genome-scale metabolic reconstructions has significantly increased, with a concomitant increase in computational effort required for their analysis. Many stoichiometric methods cannot be applied to large networks comprising several thousand reactions.

A computational analysis of stoichiometric constraints and trade-offs in cyanobacterial biofuel production.

Cyanobacteria are a promising biological chassis for the synthesis of renewable fuels and chemical bulk commodities. Significant efforts have been devoted to improve the yields of cyanobacterial products. However, while the introduction and heterologous expression of product-forming pathways is often feasible, the interactions and incompatibilities of product synthesis with the host metabolism are still insufficiently understood.