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Dirk Weuster-Botz

Publications and source records attributed to Dirk Weuster-Botz.

13 recordsLinked to original sources
PubMed2006

Model-supported optimization of phototrophic growth in a stirred-tank photobioreactor.

A fuzzy-logic light attenuation model was developed and validated for a stirred-tank photobioreactor. Based on this model, local light intensities were used to calculate local specific growth rates of the cyanobacteria Synechococcus PCC 7942. The light regime for maximization of biomass space-time yield in a batch process was estimated using a genetic algorithm taking into account the integral average of the individual growth rates.

Algorithms↗
PubMed2006

Application of fuzzy-logic models for metabolic control analysis.

A priori information or valuable qualitative knowledge can be incorporated explicitly to describe enzyme kinetics making use of fuzzy-logic models. Although restricted to linear relationships, it is shown that fuzzy-logic augmented models are not only able to capture non-linear features of enzyme kinetics but also allow the proper mathematical treatment of metabolic control analysis. The explicit incorporation of valuable qualitative knowledge is crucial, particularly when handling data estimated from in vivo kinetics studies, since this experimental information is scarce and usually contains measurement errors. Therefore, data-driven techniques, such as the one presented in this work, form a serious alternative to established kinetics approaches.

Animals↗
PubMed2006

Genetic algorithm for multi-objective experimental optimization.

A new software tool making use of a genetic algorithm for multi-objective experimental optimization (GAME.opt) was developed based on a strength Pareto evolutionary algorithm. The software deals with high dimensional variable spaces and unknown interactions of design variables. This approach was evaluated by means of multi-objective test problems replacing the experimental results. A default parameter setting is proposed enabling users without expert knowledge to minimize the experimental effort (small population sizes and few generations).

Algorithms↗
PubMed2006

Water immiscible ionic liquids as solvents for whole cell biocatalysis.

Whole cell biocatalysis can effectively be used for the production of enantiomerically pure compounds, but efficiency is often low. Toxicity and poor solubility of substrates and products are the main obstacles. In this study, water immiscible ionic liquids are shown to have no damaging effects on the cell membranes of Escherichia coli and Saccharomyces cerevisiae. Thus, they can be used as biocompatible solvents for microbial biotransformations exemplified by an increase in yield of chiral alcohol synthesis. As key point to the success of these processes, the distribution ratio of the reactants between the ionic liquid and the aqueous phase was identified. The use of ionic liquids as substrate reservoir and in situ extracting agent for the asymmetric reduction of various ketones resulted in an increase of chemical yield from <50% to 80-90% in simple batch processes. (R)-1-(4-chlorophenyl)ethanol was produced at a higher initial reaction rate in the biphasic system (>50 microM s(-1) L(-1)) compared to the aqueous system. This result demonstrates that good mass transfer rates can be obtained despite the relatively high viscosity of ionic liquids.

Biocompatible Materials↗
PubMed2006

Comparison of genetic algorithms for experimental multi-objective optimization on the example of medium design for cyanobacteria.

In this work, two different genetic algorithms were applied to improve culture media composition for the autotrophic cyanobacteria Synechococcus PCC 7942. Biomass yield and conversion of the asymmetric reduction of 2', 3', 4', 5', 6'-pentafluoroacetophenone were considered as simultaneous objectives, resulting in a multi-objective optimization problem. Even when similar performances of both algorithms were observed, it could be shown that a novel strength pareto approach was able to achieve remarkable results with a reduced number of experiments (160 instead of 320). Handling a high number of media components (13), their concentrations were adjusted, delivering high improvements in comparison to the standard BG 11 culture media. The quality of the Synechococcus biocatalyst could be increased up to fivefold compared to the initial state of the optimization.

Algorithms↗
PubMed2005

Methods and milliliter scale devices for high-throughput bioprocess design.

Based on electromagnetic simulations as well as on computational fluid dynamics simulations gas-inducing impellers and their magnetic inductive drive were optimized for stirred-tank reactors on a 10 ml-scale arranged in a bioreaction block with 48 bioreactors. High impeller speeds of up to 4,000 rpm were achieved at very small electrical power inputs (63 W with 48 bioreactors). The maxima of local energy dissipation in the reaction medium were estimated to be up to 50 W L(-1) at 2,800 rpm. Total power input and local energy dissipation are thus well comparable to standard stirred-tank bioreactors. A prototype fluorescence reader for 8 bioreactors with immobilized fluorometric sensor spots was applied for online measurement of dissolved oxygen concentration making use of the phase detection method. A self-optimizing scheduling software was developed for parallel control of 48 bioreactors with a liquid-handling system for automation of titration and sampling. It was shown on the examples of simple parallel batch cultivations of Escherichia coli with different media compositions that high cell densities of up to 16.5 g L(-1) dry cell mass can be achieved without pH-control within 5 h with a high parallel reproducibility (standard deviation<3.5%, n=48) due to the high oxygen transfer capability of the gas-inducing stirred-tank bioreactors.

Bioreactors↗
PubMed2005

Asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate with Lactobacillus kefir.

An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% (120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l(-1) h(-1). A diastereomeric excess of >99% was measured for (3R, 5S) and (3S, 5S) tert-butyl 6-chloro-dihydroxyhexanoate.

Biotechnology↗
PubMed2005

Combined sulfite method for the measurement of the oxygen transfer coefficient k(L)a in bio-reactors.

The combined sulfite method is proposed for the measurement of oxygen transfer coefficients, k(L)a, in bio-reactors. The method consists of a steady-state and a dynamic measurement which are carried out under the same experimental conditions and thus yield data for both methods during one experiment. The applied experimental conditions are shown to avoid chemical enhancement during the steady-state measurement. Moreover, no parallel sulfite oxidation occurs during the oxygen saturation phase of the dynamic measurement. Under the applied experimental conditions, no information about the sulfite oxidation kinetics is required and possible metal ion impurities in sulfite salts do not influence the measurement. The characterization of a laboratory-scale bioreactor aerated with pure oxygen yields k(L)a values during the steady-state and the dynamic measurements that are in good agreement with the dynamic pressure method, the correctness of which is generally accepted. When air is used for absorption, the steady-state measurement yields k(L)a values that correlate to the correct variant of the standard dynamic method. The dynamic measurement with air absorption yields a k(L)a value which considers the influence of the non-uniform bubble size distribution present in bubble-aerated bio-reactors.

Bioreactors↗
PubMed2005

Estimation of optimal feeding strategies for fed-batch bioprocesses.

A generic methodology for feeding strategy optimization is presented. This approach uses a genetic algorithm to search for optimal feeding profiles represented by means of artificial neural networks (ANN). Exemplified on a fed-batch hybridoma cell cultivation, the approach has proven to be able to cope with complex optimization tasks handling intricate constraints and objective functions. Furthermore, the performance of the method is compared with other previously reported standard techniques like: (1) optimal control theory, (2) first order conjugate gradient, (3) dynamical programming, (4) extended evolutionary strategies. The methodology presents no restrictions concerning the number or complexity of the state variables and therefore constitutes a remarkable alternative for process development and optimization.

Algorithms↗
PubMed2005

Parallel reactor systems for bioprocess development.

Controlled parallel bioreactor systems allow fed-batch operation at early stages of process development. The characteristics of shaken bioreactors operated in parallel (shake flask, microtiter plate), sparged bioreactors (small-scale bubble column) and stirred bioreactors (stirred-tank, stirred column) are briefly summarized. Parallel fed-batch operation is achieved with an intermittent feeding and pH-control system for up to 16 bioreactors operated in parallel on a scale of 100 ml. Examples of the scale-up and scale-down of pH-controlled microbial fed-batch processes demonstrate that controlled parallel reactor systems can result in more effective bioprocess development. Future developments are also outlined, including units of 48 parallel stirred-tank reactors with individual pH- and pO2-controls and automation as well as liquid handling system, operated on a scale of ml.

Bioreactors↗
PubMed2005

Miniature bioreactors for automated high-throughput bioprocess design (HTBD): reproducibility of parallel fed-batch cultivations with Escherichia coli.

To verify the reproducibility of cultivations of Escherichia coli in novel millilitre-scale bioreactors, fully automated fed-batch cultivation was performed in seven parallel-operated ml-scale bioreactors with an initial volume of 10 ml/reactor. The process was automatically controlled by a liquid-handling system responsible for glucose feeding, titration and sampling. Atline analysis (carried out externally of the reaction vessel with a short time delay) comprised automated pH and attenuance measurements. The partial pressure of oxygen (pO2) was measured online by a novel fluorimetric sensor block measuring the fluorescence lifetime of fluorophors immobilized inside the millilitre-scale bioreactors. Within a process time of 14.6 h, the parallel cultivation yielded a dry cell weight of 36.9+/-0.9 g.l(-1). Atline pH measurements were characterized by an S.D. of <1.1% throughout the process. Computational-fluid-dynamics simulation of single-phase flow yields a mean power input of 21.9 W.l(-1) at an impeller speed of 2800 rev./min corresponding to a power number (NP) of 3.7.

Automation↗
PubMed2004

Production of Lactobacillus kefir cells for asymmetric synthesis of a 3,5-dihydroxycarboxylate.

An efficient fedbatch process for the production of Lactobacillus kefir DSM 20587 cells was developed. An improvement in space time yield of 270% (3.7 g(DCW) l(-1)-day(-1)) and in final enzyme activity of 440% (9.1 U/ml) was achieved on a 150 l scale by controlling the oxygen transfer rate to 7--9 mmol l(-1) h(-1). The cells exhibited good and highly stereoselective reducing activities against tert-butyl 6-chloro-3,5-dioxohexanoate. tert-Butyl (3R,5S)-6-chloro-dihydroxyhexanoate, a chiral building block for HMG-CoA reductase inhibitor synthesis, was produced with 47.5% yield and >99% ee at C(3)3 and C(5)5 in a simple batch biotransformation process.

Biomass↗