Enabling Technologies: Fermentation and Downstream Processing

Weuster‐Botz, Dirk; Hekmat, Dariusch; Puskeiler, Robert; Franco‐Lara, Ezequiel

doi:10.1007/10_2006_034

Cited by 19 publications

(9 citation statements)

References 109 publications

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“…The crystals can be relatively small and the crystal growth rate should be high. Technical‐scale crystallization can be an inexpensive alternative to purification as well as polishing via chromatography, particularly for therapeutic proteins (Jacobsen et al, 1998; Schmidt et al, 2005; Takakura et al, 2006; Weber et al, 2008; Weuster‐Botz et al, 2007). Crystals have a well‐defined product morphology compared to precipitate and therefore can easily be separated by filtration (Harrison et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Protein crystallization in stirred systems—scale‐up via the maximum local energy dissipation

Smejkal

Helk

Rondeau

et al. 2013

Biotech & Bioengineering

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Macromolecular bioproducts like therapeutic proteins have usually been crystallized with µL-scale vapor diffusion experiments for structure determination by X-ray diffraction. Little systematic know-how exists for technical-scale protein crystallization in stirred vessels. In this study, the Fab-fragment of the therapeutic antibody Canakinumab was successfully crystallized in a stirred-tank reactor on a 6 mL-scale. A four times faster onset of crystallization of the Fab-fragment was observed compared to the non-agitated 10 µL-scale. Further studies on a liter-scale with lysozyme confirmed this effect. A 10 times faster onset of crystallization was observed in this case at an optimum stirrer speed. Commonly suggested scale-up criteria (i.e., minimum stirrer speed to keep the protein crystals in suspension or constant impeller tip speed) were shown not to be successful. Therefore, the criterion of constant maximum local energy dissipation was applied for scale-up of the stirred crystallization process for the first time. The maximum local energy dissipation was estimated by measuring the drop size distribution of an oil/surfactant/water emulsion in stirred-tank reactors on a 6 mL-, 100 mL-, and 1 L-scale. A comparable crystallization behavior was achieved in all stirred-tank reactors when the maximum local energy dissipation was kept constant for scale-up. A maximum local energy dissipation of 2.2 W kg(-1) was identified to be the optimum for lysozyme crystallization at all scales under study.

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Section: Introductionmentioning

confidence: 99%

Protein crystallization in stirred systems—scale‐up via the maximum local energy dissipation

Smejkal

Helk

Rondeau

et al. 2013

Biotech & Bioengineering

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“…Una versión de BR a escala de laboratorio ofrece la posibilidad de adquirir datos experimentales en tiempo real de una forma económica bajo condiciones bien controladas [9]. Para lo anterior, se requiere un software enfocado en el control en tiempo real de la operación y experimentación, de tal forma que proporcione una plataforma integrada para experimentos científicos y de investigación [10], [11].…”

Section: Introductionunclassified

Monitoring and Control System used in Microalgae Crop

Beltrán

Castro

Garces

et al. 2012

IEEE Latin Am. Trans.

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This paper presents a monitoring and control system developed with the purpose to increase the reproducibility of microalgae production processes, achieving more effectiveness of casual-analytic physiologic research, the verification of process models and the development of bioprocess. It also controls of form web the following variables: temperature and photoperiod, the equipment was tested on a Haematococcus pluvialis crop. The settings of experimentation were: photoperiod 18/6 (light hours/dark) given by the extensions of blue SMD LEDs (380<λ<470 nm), the agitation speed of 720 RPM and temperature of 24°C. The settings for the controlled crop were the same except the light that, for this case, was natural. It was found that the system is able to control automatically the process variables permitting the continuous monitoring of the experiments, removing barriers of time and place. At an institutional level, the system has brought benefits allowing the decongestion of places as saving time for both students and researchers. At a level of bioprocesses of researching, it was determined that both kinetic of microalgae growth and quantity of astaxanthin that is produced are incremented when the crop is illuminating by short wavelength, blue light.

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“…Whole-genome sequence mining (Lautru et al 2005) and genome scanning as an alternative approach, providing an efficient way to discover natural product biosynthetic gene clusters without having the complete genome sequence (Zazopoulos et al 2003); advances in microbial cell fermentation technology (Zengler et al 2005;Weuster-Botzl et al 2007) and metagenomics as a valuable alternative offering a cultivation-independent approach (Schloss and Handelsman 2005); ample successes in heterologous expression and metabolic engineering (among many others: Alper et al 2005;Schmidt et al 2005;Wenzel et al 2005;DeJong et al 2006;Julsing et al 2006;Lindahl et al 2006;Nims et al 2006;Ro et al 2006), the latter being in fact perceived as a progenitor of functional genomics and systems biology (Stephanopoulos et al 2004;Tyo et al 2007) Á to name only a few highlights.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

Staniek

Woerdenbag

Kayser

2008

Journal of Plant Interactions

131

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Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has yielded potential drug lead compounds with antibacterial, antiviral, antioxidant, insulin mimetic, anti-neurodegenerative and immunosuppressant properties. Furthermore, while being implicated in livestock neurotoxicosis, some endophyte-produced alkaloids have been shown to display insecticidal activity. The endophyte-host relationship is postulated to be a 'balanced antagonism'. Moreover, the plausibility of horizontal gene transfer (HGT) hypothesis is taken into account. Knowledge of the genetic background of endophytic natural product biosynthesis is discussed on the basis of loline alkaloids, ergopeptines, lolitrems and maytansinoids. The current dynamic progress in genomics will contribute to a better understanding of endophytic microbes and to further exploiting them as a source of pharmaceutically relevant compounds.

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Enabling Technologies: Fermentation and Downstream Processing

Cited by 19 publications

References 109 publications

Protein crystallization in stirred systems—scale‐up via the maximum local energy dissipation

Protein crystallization in stirred systems—scale‐up via the maximum local energy dissipation

Monitoring and Control System used in Microalgae Crop

Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

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