The development and application of high throughput cultivation technology in bioprocess development

Long, Quan; Liu, Xiuxia; Yang, Yankun; Li, Lü; Harvey, Linda M.; McNeil, Brian; Bai, Zhonghu

doi:10.1016/j.jbiotec.2014.03.028

Cited by 89 publications

(65 citation statements)

References 101 publications

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“…High-throughput cultivation has undergone rapid evolution in recent years in reducing culture volume, applying in-process real-time monitoring or control at the micro scale, and realizing full automation of the systems [159,160]. A number of emerging cultivation platforms has been commercialized, including microtitre plate culture, micro scale bioreactors and in-parallel fermentation systems [160]. These platforms that significantly reduce culture volume have been adopted extensively to replace shaker flasks [161].…”

Section: Escherichia Coli Expression Strains and Cell Culturementioning

confidence: 99%

“…These platforms that significantly reduce culture volume have been adopted extensively to replace shaker flasks [161]. High-throughput cultivation technology, which enables researchers to handle a large number of samples under a range of fermentation conditions in a high-throughput format, can remarkably shorten the timeline from DNA to large-scale protein production [160]. …”

Section: Escherichia Coli Expression Strains and Cell Culturementioning

confidence: 99%

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High-throughput recombinant protein expression in Escherichia coli : current status and future perspectives

Jia¹,

Jeon²

2016

Open Biol.

246

160

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The ease of genetic manipulation, low cost, rapid growth and number of previous studies have made Escherichia coli one of the most widely used microorganism species for producing recombinant proteins. In this post-genomic era, challenges remain to rapidly express and purify large numbers of proteins for academic and commercial purposes in a high-throughput manner. In this review, we describe several state-of-the-art approaches that are suitable for the cloning, expression and purification, conducted in parallel, of numerous molecules, and we discuss recent progress related to soluble protein expression, mRNA folding, fusion tags, post-translational modification and production of membrane proteins. Moreover, we address the ongoing efforts to overcome various challenges faced in protein expression in E. coli, which could lead to an improvement of the current system from trial and error to a predictable and rational design.

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Section: Escherichia Coli Expression Strains and Cell Culturementioning

confidence: 99%

Section: Escherichia Coli Expression Strains and Cell Culturementioning

confidence: 99%

High-throughput recombinant protein expression in Escherichia coli : current status and future perspectives

Jia¹,

Jeon²

2016

Open Biol.

246

160

View full text Add to dashboard Cite

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“…That means the numbers of mutants that can be analyzed at once are limited. Therefore, development of rapid and accurate screening methods is necessary for understanding the behavior of mutants [28]. Considering the main product of B .…”

Section: Resultsmentioning

confidence: 99%

Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high-throughput screening

Fan

et al. 2017

PLoS ONE

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In the present study, a novel breeding strategy of atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the uridine production of engineered Bacillus subtilis TD12np. A high-throughput screening method was established using both resistant plates and 96-well microplates to select the ideal mutants with diverse phenotypes. Mutant F126 accumulated 5.7 and 30.3 g/L uridine after 30 h in shake-flask and 48 h in fed-batch fermentation, respectively, which represented a 4.4- and 8.7-fold increase over the parent strain. Sequence analysis of the pyrimidine nucleotide biosynthetic operon in the representative mutants showed that proline 1016 and glutamate 949 in the large subunit of B. subtilis carbamoyl phosphate synthetase were of importance for the allosteric regulation caused by uridine 5′-monophosphate. The proposed mutation method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain uridine-overproducing strain.

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“…These requirements have pushed the development in automation, miniaturization, and parallelization of experimental facilities developing automatic Liquid Handling Stations (LHS) for High Throughput Screening (HTS) and High Throughput Bioprocess Design (HTBD), (Long et al, 2014;Puskeiler et al, 2005;Sch€ apper et al, 2009) as well as sensor and Process Analytical Technologies (PAT) for a better and less invasive insight into biological systems (Neubauer et al, 2013). The rapid growth of these technologies brings additional challenges, such as the correct handling and analysis of very large data sets (Kozak, 2014;Shockley, 2015) and the design of extremely complex experiments.…”

Section: Introductionmentioning

confidence: 99%

Online optimal experimental re‐design in robotic parallel fed‐batch cultivation facilities

Bournazou

Barz

Nickel

et al. 2016

Biotech & Bioengineering

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We present an integrated framework for the online optimal experimental re-design applied to parallel nonlinear dynamic processes that aims to precisely estimate the parameter set of macro kinetic growth models with minimal experimental effort. This provides a systematic solution for rapid validation of a specific model to new strains, mutants, or products. In biosciences, this is especially important as model identification is a long and laborious process which is continuing to limit the use of mathematical modeling in this field. The strength of this approach is demonstrated by fitting a macro-kinetic differential equation model for Escherichia coli fed-batch processes after 6 h of cultivation. The system includes two fully-automated liquid handling robots; one containing eight mini-bioreactors and another used for automated at-line analyses, which allows for the immediate use of the available data in the modeling environment. As a result, the experiment can be continually re-designed while the cultivations are running using the information generated by periodical parameter estimations. The advantages of an online re-computation of the optimal experiment are proven by a 50-fold lower average coefficient of variation on the parameter estimates compared to the sequential method (4.83% instead of 235.86%). The success obtained in such a complex system is a further step towards a more efficient computer aided bioprocess development. Biotechnol. Bioeng. 2017;114: 610-619. © 2016 Wiley Periodicals, Inc.

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The development and application of high throughput cultivation technology in bioprocess development

Cited by 89 publications

References 101 publications

High-throughput recombinant protein expression in Escherichia coli : current status and future perspectives

High-throughput recombinant protein expression in Escherichia coli : current status and future perspectives

Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high-throughput screening

Online optimal experimental re‐design in robotic parallel fed‐batch cultivation facilities

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