•Design and optimization of a poly(hydroxyalkanoate) production plant.•Mass and energy balances, design, sizing and cost equations.•Polymer biosynthesis using economical carbon ...sources.•Techno-economic assessment of the biopolymer process.•Economic sensitivity analysis reveals potential improvements to the bioprocess.
In this work, we propose a Mixed Integer Nonlinear Programming (MINLP) model to determine the optimal design of a poly(hydroxyalkanoate)s (PHAs) production plant configuration. The superstructure based optimization model considers different carbon sources as raw material: glycerol (crude and purified), corn starch, cassava starch, sugarcane sucrose and sugarcane molasses. The PHA extraction section includes four alternatives: the use of enzyme, solvent, surfactant-NaOCl or surfactant-chelate. Model constraints include detailed capital cost for equipment, mass and energy balances, product specifications and operating bounds on process units. The resulting MINLP model maximizes the project net present value (NPV) as objective function and it is implemented in an equation oriented environment. Optimization results show the sugarcane-enzyme option as the most promising alternative (NPV = 75.01 million USD) for PHAs production with an energy consumption of 22.56 MJ/kg PHA and a production cost of 3.02 USD/kg PHA. Furthermore, an economic sensitivity analysis is performed.
Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on ...their metabolic landscape and map connections between metabolic and genomic profiles. Combined serum and urine metabolomics improved AML characterization compared with individual biofluid analysis. At intracellular level, AML displayed dysregulated amino acid, nucleotide, lipid, and bioenergetic metabolism. The integration of intracellular and biofluid metabolomics provided a map of alterations in the metabolism of polyamine, purine, keton bodies and polyunsaturated fatty acids and tricarboxylic acid cycle. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis. Interestingly, integrated genomic-metabolic profiles defined two subgroups of NPM1-mut AML. One was enriched for mutations in cohesin/DNA damage-related genes (NPM1/cohesin-mut AML) and showed increased serum choline + trimethylamine-N-oxide and leucine, higher mutation load, transcriptomic signatures of reduced inflammatory status and better ex-vivo response to EGFR and MET inhibition. The transcriptional differences of enzyme-encoding genes between NPM1/cohesin-mut and NPM1-mut allowed in silico modeling of intracellular metabolic perturbations. This approach predicted alterations in NAD and purine metabolism in NPM1/cohesin-mut AML that suggest potential vulnerabilities, worthy of being therapeutically explored.
Argentina's petrochemicals industry was launched during World War II, with the establishment of two pioneering Latin American operations. In 1942, Argentina's Ministry of Defense and its General ...Directorate of Military Industries (DGFM) opened the first petrochemical plant in Argentina, which produced toluene for use in trinitrotoluene (TNT). In 1944, YPF began to produce isopropyl alcohol from propylene at a 1,200-ton/yr plant.
Cyanobacteria have been considered as promising candidates for sustainable bioproduction from inexpensive raw materials, as they grow on light, carbon dioxide, and minimal inorganic nutrients. In ...this study, we present a genome‐scale metabolic network model for Synechocystis sp. PCC 6803 and study the optimal design of the strain for ethanol production by using a mixed integer linear problem reformulation of a bilevel programming problem that identifies gene knockouts which lead to coupling between growth and product synthesis. Five mutants were found, where the in silico model predicts coupling between biomass growth and ethanol production in photoautotrophic conditions. The best mutant gives an in silico ethanol production of 1.054 mmol·gDW
−1·h
−1.
Rational design of growth‐coupled ethanol producing strains of the cyanobacteria Synechocystis sp. PCC 6803 was performed in silico by applying bilevel optimization techniques to a genome‐ scale metabolic network model. Solutions that couple ethanol production to growth were identified and evaluated with MOMA and in a bioreactor model, with positive results that encourage the in vivo implementation of the coupled mutants for photoautotrophic production of fourth generation biofuels.
Poly(3-hydroxybutyrate) (PHB), a biopolymer similar to polypropylene, is currently produced by heterotrophic bacteria. However, the elevated cost of raw material used as carbon and energy sources are ...promoting the development of new sustainable bioprocess based on photoautotrophic routes costs. In unbalanced growth conditions, some cyanobacteria can accumulate PHB using CO2 as the sole carbon source, becoming an option for PHB production. In this work, we study in silico PHB production with the model cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). We consider two different strategies for in silico strain design: coupled growth-PHB production and a two-stage fermentation strategy. For both strategies we consider a GEnome-scale Model (GEM) of Synechocystis, which was modified to account for PHB production. The coupled approach relies on a bilevel optimization problem that identifies gene knock-outs needed to obtain a mutant that couples PHB production with biomass formation. For this case, two mutants that successfully achieve the required coupling are obtained, and the best one is analyzed in terms of intervention strategies, flux distributions and productivities. For the two-stage fermentation strategy, we consider two bioreactors in series. The first one is optimized for biomass production under balanced growth conditions, and the second one is optimized for PHB production under nitrogen starvation conditions. Both stages are simulated within dfba, a python tool for solving the Dynamic Flux Balance Analysis (DFBA) problem which provides the solution of a bioreactor model subject to the mass balances of the GEM. Numerical results for the two-stage approach provide a PHB concentration of 4.764 g PHB/L while the mutant provides a lower concentration of 0.391 g PHB/L. Nevertheless, both strategies provide high PHB content per cell dry weight (cdw), which makes results attractive for photosynthetic PHB production.
•Synechocystis metabolic modelling for poly-β-hydroxybutyrate production assessment•Two strategies: coupled growth-PHB production and two-stage fermentation•In silico mutants with fully coupled PHB production obtained•Two-stage fermentation under nitrogen starvation shows higher PHB accumulation than coupled mutants.•Numerical results show high PHB content per cell dry weight for both strategies.
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•Sunflower oil hydrolysis reaction was catalyzed by castor bean lipase powder.•The reaction was tested at different times, temperatures, and lipase concentrations.•Lipase thermal ...inactivation was obtained at temperatures higher than 37°C.•Experimental data were fitted by two mathematical models.•The behavior of intermediate and final reaction products was satisfactorily modeled.
This work provides experimental data and mathematical modeling of the hydrolysis reaction of high oleic sunflower oil catalyzed by lipase powder (LP) from castor bean seeds. The production of fatty acids (FA) at different times (0.5–48h), temperatures (30–50°C) and concentrations of LP (0.006 and 0.012gLP/goil) was experimentally tested. As expected, an increase in LP concentration and reaction temperature caused an increase of the initial reaction rate. The highest FA concentrations at long reaction times were obtained using 30 and 37°C, while 45 and 50°C showed a marked lipase thermal inactivation. Despite this, thermal inactivation effects were still detected at 37°C using 0.006gLP/goil, although undetected at the highest tested LP concentration. Two mathematical models were used to fit the experimental data in order to analyze FA production at tested conditions. The first one was a hyperbolic empirical model for FA concentration as a function of reaction time, which permitted the estimation of initial reaction rates and comparisons with similar reaction systems. Furthermore, a first principles model of a chain reaction system, including temperature inactivation, was also applied and kinetic constants were estimated as Arrhenius-type temperature functions. Results showed that both proposed models provided good mathematical representations of the hydrolysis reaction of high oleic sunflower oil catalyzed by LP from castor bean at the specific studied conditions. Although the second one is far more complex, it allows to predict the behavior at different conditions within the analyzed ranges, describing not only the final product (FA) but also the intermediate ones. Furthermore, this proposed first principles model was successfully validated against published experimental data. Thus, depending on the requirements and available data, both models could be helpful tools to represent and/or study the hydrolysis catalyzed by lipases from castor bean seeds.
In this work, we propose a genomic scale metabolic network model of the genetically engineered Synechocystis sp. PCC 6803 within a bilevel programming framework to study ethanol photosynthetic ...production. The model is studied under carbon limiting conditions with restricted photon flux. Maximum biomass and ethanol theoretical productions are obtained using flux balance analysis for the decoupled case. Furthermore, we formulate a bilevel programming problem, reformulated into a mixed integer linear problem (MILP), to study the possibility of coupling cell growth with ethanol production. Models are formulated within an equation-oriented framework in GAMS.
Numerical results provide useful insights on ethanol production by this strain within the context of genomic-scale cyanobacterial metabolism.
In this work we address dynamic optimization of ethanol production by Dynamic Flux Balance Analysis in an engineered cyanobacterium with autotrophic growth (i.e., using CO2 as substrate). The ...photobioreactor optimization model is integrated to the metabolic network one by replacing the inner problem by its first order optimality conditions. Complementarity constraints that arise associated to the optimality conditions are efficiently handled with a penalty function formulation. Numerical results suggest the possibility to activate the ethanol production pathway after 20h in the batch run to enhance ethanol production.
Ethanol has been studied extensively as one of the current and probably future energy vectors. Fermentation of hydrolysed oligosaccharides from macroalgae biomass to ethanol has been certified, and ...several processing options have been proposed. In the present work, we model the production of ethanol based on Laminaria, a seaweed genus that belongs to the so-called “brown algae” group, as the carbon source. In brown algae, the most relevant sugars that can be used as substrate for fermentation are mannitol -the alcohol form of the sugar mannose- and laminaran, a linear polysaccharide of (1,3)-ß-D- glucopyranose. We consider the yeast Pichia angophorae as the fermenting microorganism. The model includes dynamic mass balances for biomass, ethanol, mannitol and laminaran. Growth is controlled via limiting functions that modify the biomass equation for temperature and oxygen transfer rate (OTR). It is also modified by including a term that considers inhibition by ethanol. Based on the proposed model, a dynamic parameter estimation problem is formulated, the objective function being weighted least-squares fit to data, subject to the mass balance equations. The data set for parameter estimation was obtained in batch liquid cultures, with experiments performed over 40 hours. Numerical results provide useful insights on ethanol production using macroalgae biomass as carbon source.
Discutir a necessidade de implantar alguma ferramenta à avaliação de desempenho em algum programa social, a exemplo dos Centros de Referência de Atendimento Social (CRAS) faz com que administração ...reflita sobre o valor gerado pelo seu desempenho e permite que sejam realizadas análises e mudanças (se necessário) dentro de uma proposta de gestão eficiente; todo programa social deve estar ancorado em noções de causalidade, ou seja, várias relações causais que indicam a geração de benefícios com algum processo, visando a transformação social desejada pelas interferências nas condições e na qualidade de vida dos usuários. Pela metodologia da pesquisa bibliográfica e na linha exploratória, consultando autores e produções a respeito do contexto que o tema encerra. Viu-se que, sim, é significativa a avaliação de desempenho sobre os serviços e ações que elevam, dentro do possível, a qualidade de vida das famílias/usuários em situação de vulnerabilidade, cujo artigo discorreu desde a rápida historicidade dos CRAS até a intervenção que confere ao tema uma forma de trabalhar melhores configurações tanto na gestão quanto na satisfação dos que dele dependem ou recorrem, o que é fundamental exercer essa articulação entre trabalho interno e resultados externos a partir do que a transparência na administração pública apregoa: tornar evidente as ações e reparar os erros/falhas para a possibilidade de eficiência.
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