Optimal 1,3-propanediol production: Exploring the trade-off between process yield and feeding rate variation

This paper proposes a new optimal control model for the production of 1,3-propanediol (1,3-PD) viamicrobial fed-batch fermentation. The proposed model is governed by a nonlinear multi stage dynamic system with two modes: feeding mode, in which glycerol and alkali substrates are added continuously to the fermentor; and batch mode, in which no substrates are added to the fermentor. The non-standard objective function incorporates both the final 1,3-PD yield and the cost of changing the input feeding rate, which is the control variable for the fed-batch fermentation process. Continuous state inequality constraints are imposed to ensure that the concentrations of biomass, glycerol, and reaction products lie within specified limits. Using the constraint transcription method, we approximate the continuous state inequality constraints by a conventional inequality constraint to yield an approximate parameter optimization problem. We then develop a combined particle swarm and gradient-based optimization algorithm to solve this approximate problem. The paper concludes with simulation results

Optimization of a fed-batch bioreactor for 1,3-propanediol production using hybrid nonlinear optimal control

A nonlinear hybrid system was proposed to describe the fed-batch bioconversion of glycerol to 1,3-propanediol with substrate open loop inputs and pH logic control in previous work [47]. The current work concerns the optimal control of this fed-batch process. We slightly modify the hybrid system to provide a more convenient mathematical description for the optimal control of the fed-batch culture. Taking the feeding instants and the terminal time as decision variables, we formulate an optimal control model with the productivity of 1,3-propanediol as the performance index. Inequality path constraints involved in the optimal control problem are transformed into a group of end-point constraints by introducing an auxiliary hybrid system. The original optimal control problem is associated with a family of approximation problems. The gradients of the cost functional and the end-point constraint functions are derived from the parametric sensitivity system. On this basis, we construct a gradient-based algorithm to solve the approximation problems. Numerical results show that the productivity of 1,3-propanediol can be increased considerably by employing our optimal control policy

Application of Continuous Culture Methods to Recombinant Protein Production in Microorganisms

Depending on the environmental conditions, cells adapt their metabolism and specific growth rate. Rearrangements occur on many different levels such as macromolecular composition, gene and protein expression, morphology and metabolic flux patterns. As the interplay of these processes also determines the output of a recombinant protein producing system, having control over specific growth rate of the culture is advantageous. Continuous culture methods were developed to grow cells in a constant environment and have been used for decades to study basic microbial physiology in a controlled and reproducible manner. Our review summarizes the uses of continuous cultures in cell physiology studies and process development, with a focus on recombinant protein-producing microorganisms

Process development of propionic acid production by fermentation

The fermentation kinetics of Propionibacterium thoenii strain P20 were studied with calcium alginate bead-immobilized cells without mass transfer limitations. The fermentation was found to be significantly affected by the end-product, propionic acid, in the medium. High levels of the acid not only inhibited cell growth, but also changed cell metabolism to produce more byproducts such as acetic, succinic and lactic acids. As a result, substrate consumption rate and propionic acid productivity and yield also decreased;Coupling liquid-liquid extraction of the acid with the fermentation, that is, extractive fermentation, alleviated the inhibitory effects. Solvent selection, based on partitioning and toxicity, was carried out among three solvent systems: Alamine°ler 304-1 in 2-octanol, 1-dodecanol, and Witcohol°ler 85 NF (oleyl alcohol). For each system, the acid loading per amine molecule decreased with increasing amine concentration; hence, an optimal amine concentration existed. The solvent toxicity to five strains of propionibacteria was determined. Strain P20 was the most solvent-resistant strain and Alamine 304-1 in Witcohol 85 NF was the only nontoxic solvent. Addition of vegetable oils to scavenge the toxic diluents was also able to reduce toxicity;Extractive fermentation was carried out with 40% (w/v) bead load of immobilized P20 cells and a hollow-fiber membrane extractor. By maintaining the propionic acid concentration at about 13 g/L, the yields of propionic and acetic acids were more than doubled compared to those of the nonextractive process. Higher acid productivities, an 80% reduction of base consumption for pH control, and solvent selectivity of propionic over acetic acid were also achieved;Vacuum distillation produced purified acids as the overheads and recyclable solvent as the bottoms. No solvent degradation occurred under the distillation conditions;Based on the experimental findings, economic evaluations of the extractive fermentation process on a 50,000-ton annual production scale were conducted. The process was modified to use whole-cell extraction with a mixer-settler extractor. This process suggested that economic feasibility could only be realized with favorable assumptions such as long-term bead usage, byproduct revenue, and inexpensive substrate

Optimal Control of Nonlinear Switched Systems: Computational Methods and Applications

A switched system is a dynamic system that operates by switching between different subsystems or modes. Such systems exhibit both continuous and discrete characteristics—a dual nature that makes designing effective control policies a challenging task. The purpose of this paper is to review some of the latest computational techniques for generating optimal control laws for switched systems with nonlinear dynamics and continuous inequality constraints. We discuss computational strategiesfor optimizing both the times at which a switched system switches from one mode to another (the so-called switching times) and the sequence in which a switched system operates its various possible modes (the so-called switching sequence). These strategies involve novel combinations of the control parameterization method, the timescaling transformation, and bilevel programming and binary relaxation techniques. We conclude the paper by discussing a number of switched system optimal control models arising in practical applications

Book of abstracts of the 10th International Chemical and Biological Engineering Conference: CHEMPOR 2008

This book contains the extended abstracts presented at the 10th International Chemical and Biological Engineering Conference - CHEMPOR 2008, held in Braga, Portugal, over 3 days, from the 4th to the 6th of September, 2008. Previous editions took place in Lisboa (1975, 1889, 1998), Braga (1978), Póvoa de Varzim (1981), Coimbra (1985, 2005), Porto (1993), and Aveiro (2001). The conference was jointly organized by the University of Minho, “Ordem dos Engenheiros”, and the IBB - Institute for Biotechnology and Bioengineering with the usual support of the “Sociedade Portuguesa de Química” and, by the first time, of the “Sociedade Portuguesa de Biotecnologia”. Thirty years elapsed since CHEMPOR was held at the University of Minho, organized by T.R. Bott, D. Allen, A. Bridgwater, J.J.B. Romero, L.J.S. Soares and J.D.R.S. Pinheiro. We are fortunate to have Profs. Bott, Soares and Pinheiro in the Honor Committee of this 10th edition, under the high Patronage of his Excellency the President of the Portuguese Republic, Prof. Aníbal Cavaco Silva. The opening ceremony will confer Prof. Bott with a “Long Term Achievement” award acknowledging the important contribution Prof. Bott brought along more than 30 years to the development of the Chemical Engineering science, to the launch of CHEMPOR series and specially to the University of Minho. Prof. Bott’s inaugural lecture will address the importance of effective energy management in processing operations, particularly in the effectiveness of heat recovery and the associated reduction in greenhouse gas emission from combustion processes. The CHEMPOR series traditionally brings together both young and established researchers and end users to discuss recent developments in different areas of Chemical Engineering. The scope of this edition is broadening out by including the Biological Engineering research. One of the major core areas of the conference program is life quality, due to the importance that Chemical and Biological Engineering plays in this area. “Integration of Life Sciences & Engineering” and “Sustainable Process-Product Development through Green Chemistry” are two of the leading themes with papers addressing such important issues. This is complemented with additional leading themes including “Advancing the Chemical and Biological Engineering Fundamentals”, “Multi-Scale and/or Multi-Disciplinary Approach to Process-Product Innovation”, “Systematic Methods and Tools for Managing the Complexity”, and “Educating Chemical and Biological Engineers for Coming Challenges” which define the extended abstracts arrangements along this book. A total of 516 extended abstracts are included in the book, consisting of 7 invited lecturers, 15 keynote, 105 short oral presentations given in 5 parallel sessions, along with 6 slots for viewing 389 poster presentations. Full papers are jointly included in the companion Proceedings in CD-ROM. All papers have been reviewed and we are grateful to the members of scientific and organizing committees for their evaluations. It was an intensive task since 610 submitted abstracts from 45 countries were received. It has been an honor for us to contribute to setting up CHEMPOR 2008 during almost two years. We wish to thank the authors who have contributed to yield a high scientific standard to the program. We are thankful to the sponsors who have contributed decisively to this event. We also extend our gratefulness to all those who, through their dedicated efforts, have assisted us in this task. On behalf of the Scientific and Organizing Committees we wish you that together with an interesting reading, the scientific program and the social moments organized will be memorable for all.Fundação para a Ciência e a Tecnologia (FCT

Production of Astaxanthin Using Modified E. coli Cells

There are several promising markets for naturally synthesized Astaxanthin, a carotenoid found in krill, shrimp, salmon, and other marine life that imparts to these creatures a pink coloring of the flesh and has demonstrated human health-promoting anti-inflammatory and antioxidant activity. Compared to Astaxanthin produced through chemical synthesis, Astaxanthin synthesized through natural fermentative processes (in yeast and algae) is esterified, imparting greater antioxidant activity as well as bioavailability and making it the preferred ingredient for nutraceutical formulations. Additionally, as consumer preferences trend toward natural production processes free from the use of petrochemical solvents which may pose hazards to health hazards, fermentative production coupled with an extraction process featuring more environment- and health-friendly solvents is desired. Recently, a strain of E.coli has been genetically optimized to produce Astaxanthin, offering a cheaper synthesis route compared with algal cultivation. Herein, the authors propose a process for the production of natural Astaxanthin through fermentation in genetically modified E.coli and recovery of the compound from biomass via supercritical CO2 extraction. The fermentation seed train is composed of three pre-seed, two seed, and three production fed-batch fermenters. Biomass from the production stage is collected in a harvest/surge tank for continuous downstream processing. The biomass is concentrated in broth, the cells are lysed, and the slurry of lysed cells are dried. The lysis product is loaded with fructose and diatomaceous earth in order to produce biomass pellets that are appropriate for the extraction phase. Supercritical CO2 with ethanol co-solvent is used to extract Astaxanthin from these pellets. Astaxanthin is heat-sensitive and has low accumulation in cells. Despite the expensive equipment necessary to preserve the structure and activity of the product and the low yearly production rate, the high selling price of Astaxanthin makes this process economically profitable, with an investor’s rate of return of 125%, net present value of $468 million, and return on investment of 171%

Effect of Bioreactor Mode of Operation on Mixed-Acid Fermentations

Using mixed-culture fermentation, the carboxylate platform produces carboxylic acids, which are chemically converted into chemicals and fuels. To optimize the mixed-acid fermentation, different bioreactor configurations and operating modes were investigated. Intermittent air exposure did not affect fermentation performance and bacterial profiles, but reduced the high-molecular-weight carboxylic acids. The microbial flora contained strict and facultative microbes, suggesting the presence of a facultative anaerobic community existing in a biofilm. Compared to countercurrent trains, propagated fixed-bed fermentations have similar selectivity and acid distribution, but lower yield, conversion, productivity, and acid concentration. One- to six-stage countercurrent fermentations were operated with similar conditions. Fewer stages increased conversion, whereas more stages increased acid concentration and selectivity. One to four stages achieved similar yield, and four to six stages achieved similar maximum acid concentration. Maximum conversion was achieved with a single stage. Recycling residual biomass retained microorganisms and nutrients and increased yield and productivity. Relative to lower biomass reflux, higher reflux increased conversion, decreased selectivity, and did not affect yield. The recommended carbon-nitrogen ratio is ~24 g carbon/g nitrogen. In four-stage fermentations, recycle to the second fermentor and in parallel to the first three fermentors was optimal. Fermentations with excess or insufficient nitrogen had higher selectivity, but decreased yield and conversion. The glucose-utilization assay is a rapid and repeatable method for determining the amount of microbial activity in a sample. This method determined ~25% efficiency of a new cell separation method. In continuous fermentation, compared to no cell recycle, recycling cellular biomass increased selectivity and yield, but decreased conversion. Compared to lower cell reflux, higher reflux increased productivity, yield, and conversion, but decreased selectivity. Compared to residual biomass recycle, cell recycle had increased selectivity and yield, but decreased conversion. A new method to screen and rank inoculum sources from natural environments was successfully developed and tested