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Bioprocess

About: Bioprocess is a research topic. Over the lifetime, 2219 publications have been published within this topic receiving 50972 citations.


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Journal ArticleDOI
TL;DR: C. glutamicum was found to have a higher tolerance to 4-HBA toxicity than previously reported hosts used for the production of genetically engineered 4- HBA, and a novel final reaction enzyme possessing characteristics superior to those in previously employed microbial 4-hBA production was screened for.
Abstract: Corynebacterium glutamicum was metabolically engineered to produce 4-hydroxybenzoic acid (4-HBA), a valuable aromatic compound used as a raw material for the production of liquid crystal polymers and paraben. C. glutamicum was found to have a higher tolerance to 4-HBA toxicity than previously reported hosts used for the production of genetically engineered 4-HBA. To obtain higher titers of 4-HBA, we employed a stepwise overexpression of all seven target genes in the shikimate pathway in C. glutamicum Specifically, multiple chromosomal integrations of a mutated aroG gene from Escherichia coli, encoding a 3-deoxy-d-arabinoheptulosonic acid 7-phosphate (DAHP) synthase, and wild-type aroCKB from C. glutamicum, encoding chorismate synthase, shikimate kinase, and 3-dehydroquinate synthase, were effective in increasing product titers. The last step of the 4-HBA biosynthesis pathway was recreated in C. glutamicum by expressing a highly 4-HBA-resistant chorismate pyruvate-lyase (UbiC) from the intestinal bacterium Providencia rustigianii To enhance the yield of 4-HBA, we reduced the formation of by-products, such as 1,3-dihydroxyacetone and pyruvate, by deleting hdpA, a gene coding for a haloacid dehalogenase superfamily phosphatase, and pyk, a gene coding for a pyruvate kinase, from the bacterial chromosome. The maximum concentration of 4-HBA produced by the resultant strain was 36.6 g/liter, with a yield of 41% (mol/mol) glucose after incubation for 24 h in minimal medium in an aerobic growth-arrested bioprocess using a jar fermentor. To our knowledge, this is the highest concentration of 4-HBA produced by a metabolically engineered microorganism ever reported.IMPORTANCE Since aromatic compound 4-HBA has been chemically produced from petroleum-derived phenol for a long time, eco-friendly bioproduction of 4-HBA from biomass resources is desired in order to address environmental issues. In microbial chemical production, product toxicity often causes problems, but we confirmed that wild-type C. glutamicum has high tolerance to the target 4-HBA. A growth-arrested bioprocess using this microorganism has been successfully used for the production of various compounds, such as biofuels, organic acids, and amino acids. However, no production method has been applied for aromatic compounds to date. In this study, we screened for a novel final reaction enzyme possessing characteristics superior to those in previously employed microbial 4-HBA production. We demonstrated that the use of the highly 4-HBA-resistant UbiC from the intestinal bacterium P. rustigianii is very effective in increasing 4-HBA production.

60 citations

Journal ArticleDOI
TL;DR: The study considerably extends the use of NIRS in fermentation processes to high cell density complex industrial production processes, and comments on how this further developments the technology towards routine in situ N IRS monitoring of bioprocesses.

59 citations

Journal ArticleDOI
TL;DR: In this review, fast on-line detection methods for this purpose are presented including different recognition and transducer strategies.
Abstract: Detecting cells and microorganisms in different matrices is becoming an increasingly important task in a variety of fields including bioprocess control, food technology, health care, and environmental analysis. In this review, fast on-line detection methods for this purpose are presented including different recognition and transducer strategies.

59 citations

Journal ArticleDOI
TL;DR: An improved expression system is available as an alternative to commonly used cell cultures for the production of recombinant proteins, based on yeast extract and buffer salts for the development of a serum‐free but hemin containing medium.
Abstract: -1 is obtained in an alternative medium, the YE-medium. For the newly developed medium, the successful expression of enhanced green fluorescent protein and the adaptation of the cultivation from the agitated culture to the bioreactor could be shown. Furthermore, an analytical method for detection of the essential, organic iron source hemin was established. The consumption of hemin was monitored because hemin is a potentially important process parameter for bioprocess control. With knowledge of these results, an improved expression system is available as an alternative to commonly used cell cultures for the production of recombinant proteins.

59 citations

Journal ArticleDOI
TL;DR: This review summarizes recent progress and current status of bioprocess monitoring and indicates that the spectrometric methods are making headway in cell culture process monitoring.
Abstract: The productivity of cell culture manufacturing for biologics has increased momentously in the past decades. Increasingly, the process research efforts are devoted into improving product quality and consistency. Consistent process performance and successful implementation of quality by design practice requires well-utilized process analytical technology. This review summarizes recent progress and current status of bioprocess monitoring. Many sensors for bioprocess monitoring have been available for decades while new ones, especially spectrometric sensors, are making their way into cell culture bioprocesses. On-line sampling devices have grown mature in the past decade thus making many instruments traditionally used for off-line analysis available for at-line use. With a general trend of using better defined medium for cell cultivation and increasing emphasis of process analytical tools, the spectrometric methods are also making headway in cell culture process monitoring. The integration of those sensing technologies will be important to advance the real-time monitoring of the state of cellular physiology for the control for process consistency and product quality.

59 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023331
2022785
2021165
2020153
2019159
2018127