Substrate Controlled Fed‐Batch Production of <scp>l</scp>‐Lysine with <i>Corynebacterium glutamicum</i>

Weuster‐Botz, Dirk; Kelle, Ralf; Frantzen, M.; Wandrey, Christian

doi:10.1021/bp970034j

Cited by 33 publications

(12 citation statements)

References 28 publications

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“…In current applications C. glutamicum is mainly used for production of small metabolites from primary metabolism, e.g. lysine [38], glutamate [39], valine [40] or succinate [41] and the published cultivation media have been optimized in the past for fast growth and amino acid production [42-44]. But during the last 5 years C. glutamicum gains in importance as a host for secretory protein production.…”

Section: Resultsmentioning

confidence: 99%

An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform

et al. 2012

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BackgroundHigh-throughput methods are widely-used for strain screening effectively resulting in binary information regarding high or low productivity. Nevertheless achieving quantitative and scalable parameters for fast bioprocess development is much more challenging, especially for heterologous protein production. Here, the nature of the foreign protein makes it impossible to predict the, e.g. best expression construct, secretion signal peptide, inductor concentration, induction time, temperature and substrate feed rate in fed-batch operation to name only a few. Therefore, a high number of systematic experiments are necessary to elucidate the best conditions for heterologous expression of each new protein of interest.ResultsTo increase the throughput in bioprocess development, we used a microtiter plate based cultivation system (Biolector) which was fully integrated into a liquid-handling platform enclosed in laminar airflow housing. This automated cultivation platform was used for optimization of the secretory production of a cutinase from Fusarium solani pisi with Corynebacterium glutamicum. The online monitoring of biomass, dissolved oxygen and pH in each of the microtiter plate wells enables to trigger sampling or dosing events with the pipetting robot used for a reliable selection of best performing cutinase producers. In addition to this, further automated methods like media optimization and induction profiling were developed and validated. All biological and bioprocess parameters were exclusively optimized at microtiter plate scale and showed perfect scalable results to 1 L and 20 L stirred tank bioreactor scale.ConclusionsThe optimization of heterologous protein expression in microbial systems currently requires extensive testing of biological and bioprocess engineering parameters. This can be efficiently boosted by using a microtiter plate cultivation setup embedded into a liquid-handling system, providing more throughput by parallelization and automation. Due to improved statistics by replicate cultivations, automated downstream analysis, and scalable process information, this setup has superior performance compared to standard microtiter plate cultivation.

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Section: Resultsmentioning

confidence: 99%

An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform

et al. 2012

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“…They are particularly well suited to cultivations that exhibit substrate inhibition, catabolite repression, toxic precursors or the glucose effect, thus improving the production of bioproducts [28]. However, relatively few studies have focused on the fed-batch cultivation of C. glutamicum [11,23,27]. And there have been no such reports on the biosynthesis of flocculants yet.…”

Section: Introductionmentioning

confidence: 99%

Fed-batch production of a bioflocculant from Corynebacterium glutamicum

Lü

et al. 2010

J Ind Microbiol Biotechnol

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The constant-rate fed-batch production of the polygalacturonic acid bioflocculant REA-11 was studied. A controlled sucrose-feeding strategy resulted in a slight improvement in biomass and a 7% reduction in flocculating activity compared with the batch process. When fed with a 3 g l(-1) urea solution, the flocculating activity was enhanced to 720 U ml(-1) in 36 h. High cell density (2.12 g l(-1)) and flocculating activity (820 U ml(-1)) were obtained in a 10-l fermentor by feeding with a sucrose-urea solution, with values of nearly two times and 50% higher than those of the batch process, respectively. Moreover, the residual sucrose declined to 2.4 g l(-1), and residual urea decreased to 0.03 g l(-1). Even higher flocculating activity of 920 U ml(-1) and biomass of 3.26 g l(-1) were obtained by feeding with a sucrose-urea solution in a pilot scale fermentation process, indicating the potential industrial utility of this constant-rate feeding strategy in bioflocculant production by Corynebacterium glutamicum.

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“…In fed-batch fermentation the dosage of the feed solution is controlled by substrate depletion signals (according to [182]). The increase of pH and pO 2 over a threshold value trigger another feed pulse, the resulting sugar concentration in the fermentation broth remains below 2 g L -1 [189]. Further improvement of the product yield to 0.38 mol mol -1 as a consequence of increased growth linked lysine formation was achieved by introduction of glucose limitation in the preculture which might lead to the activation of glucose-starvation-stimulons as was observed for E. coli [190].…”

Section: Physiological State Estimation and Optimization Of Nutrient mentioning

confidence: 95%

Microbial Production of l-Amino Acids

Faurie¹,

Thommel²,

Bathe³

2002

Advances in Biochemical Engineering/Biotechnology

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Advances in Biochemical Engineering/Biotechnology reviews actual trends in modern biotechnology. Its aim is to cover all aspects of this interdisciplinary technology where knowledge, methods and expertise are required for chemistry, biochemistry, microbiology, genetics, chemical engineering and computer science. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. They give the state-of-the-art of a topic in a comprehensive way thus being a valuable source for the next 3-5 years. It also discusses new discoveries and applications.In general, special volumes are edited by well known guest editors. The managing editor and publisher wilt however always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English.In references Advances in Biochemical Engineering/Biotechnology is abbreviated asAdv Biochem Engin/Biotechnot as a journal.A complete list of all enzymes entries either as an alphabetical Name Index or as the EC-Number Index is available at the above mentioned URL. You can download and print them free of charge.A complete list of all synonyms (more than 25,000 entries) used for the enyzmes is available in print form, ISBN 3-540-41830-X. Save 15 %We recommend a standing order for the series to ensure you automatically receive all volumes and all supplements and save 15% on the list price.Preface XI Due to the comparably high prices, L-tryptophan, which is an important pharmaceutical active ingredient produced by Ajinomoto and Amino GmbH, has been launched in the feed market in smaller quantities so far.Ajinomoto however announced in 2001 the intention to increase the annual rate to more than 1,000 tons. This is a very good example of the close interdependence between the cost of production, the target price and the amount of amino acid consumed in order to reduce primary feed stuff for animal farming.Roughly estimated, there is an inverse proportional linear relationship between the logarithm of the market price and the annual production of each amino acid. This observation forces each amino acid manufacturer to construct more efficient bacterial strains and to optimize corresponding fermentation protocols allowing a maximal specific product-and space-time-yield in order to minimize variable and fixed costs of production. This has become possible by application of the modern techniques offered by modern molecular biology and biotechnology, including the use of recombination combined with metabolic flux analysis and functional genomics.The authors of this special volume of "Advances in Biochemical Engineering/Biotechnology" have contributed significantly to the progress of amino acid biotechnology in the last decades and earn our special gratitude and admiration for their expert review articles.In order to understand the impact of the economical aspect of amino acid production we have rounded off this volume with an article dealing with this topic.Frellstedt,

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Substrate Controlled Fed‐Batch Production of l‐Lysine with Corynebacterium glutamicum

Cited by 33 publications

References 28 publications

An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform

An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform

Fed-batch production of a bioflocculant from Corynebacterium glutamicum

Microbial Production of l-Amino Acids

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