Comparative Fermentation

Hellwig, Stephan; Stöckmann, Christoph; Gellissen, Gerd; Büchs, Jochen

doi:10.1002/3527603670.ch14

Cited by 12 publications

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“…For all other methylotrophic yeast species an inductive activation of such promoters has been stated that is strictly dependent on the presence of methanol [ 17 ]. As a consequence several H. polymorpha -based industrial fermentation processes have been defined that lean on glucose or glycerol supplementation in suitable concentrations to a culture broth without any methanol additions [ 1 , 25 , 26 ].…”

Section: H Polymorpha -Based Processes Under Control Of mentioning

confidence: 99%

“…The commercial success of a recombinant product does not depend only on the characteristics of the microbial host but also to a large extent on the definition of efficient fermentation processes. In case of H. polymorpha , a defined minimal mineral medium has been developed designated SYN6 [ 25 , 32 ]. It is composed of salts, vitamins and trace elements to support growth to high cell densities and it has to be adjusted to appropriate pH conditions and has to be supplemented with suitable carbon sources (for details of components see [ 32 ]).…”

Section: H Polymorpha -Based Processes Under Control Of mentioning

confidence: 99%

“…Prior to any practical experiment, YMM ammonium concentration of the standard medium was raised from 2.2 mmol N/g glucose to 4.6 mmol N/g glucose since theoretical material balancing revealed a severe lack of nitrogen with regard to the average nitrogen content of yeast. The culture broth was additionally supplemented with calcium and iron in higher concentrations as well as with MES (2-[N-morpholino]ethanesulfonic acid) for buffering to result in YMM* [ 25 ]. Despite nitrogen addition to YMM, the respective cultures remained limited as shown representatively for A. adeninivorans LS3 in Fig.…”

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

“… Assessment of minimal media for Arxula adeninivorans LS3 by measuring respiration rates in shake flask cultures (for operating conditions and media formulation see [ 25 ] ) . Original YMM (black circles), containing poor concentrations of calcium (0.338 mg/L) and iron (0.041 mg/L), led to poor culture respiration rates below 10 mmol/(L*h).…”

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

“…The high nutrient concentrations of standard SYN6 remained unchanged. Again, the pH of SYN6 had to be buffered with MES (SYN6-MES, see [ 25 ] for detailed description) for pH stabilization between 6.4 and 5.3. Fig.…”

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

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Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment

et al. 2009

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A range of industrial H. polymorpha-based processes exist, most of them for the production of pharmaceuticals. The established industrial processes lean on the use of promoters derived from MOX and FMD, genes of the methanol metabolism pathway. In Hansenula polymorpha these promoters are de-repressed upon depletion of a range of carbon sources like glucose and glycerol instead of being induced by methanol as reported for other methylotrophs. Due to these characteristics screening and fermentation modes have been defined for strains harbouring such expression control elements that lean on a limited supplementation of glycerol or glucose to a culture medium. For fermentation of H. polymorpha a synthetic minimal medium (SYN6) has been developed. No industrial processes have been developed so far based on Arxula adeninivorans and only a limited range of strong promoter elements exists, suitable for heterologous gene expression. SYN6 originally designed for H. polymorpha provided a suitable basis for the initial definition of fermentation conditions for this dimorphic yeast. Characteristics like osmo-and thermotolerance can be addressed for the definition of culture conditions. Hansenula polymorpha and Arxula adeninivorans and their competitive environmentIn the last three decades a wide range of recombinant proteins, especially pharmaceuticals, have been produced based on heterologous gene expression in bacterial organisms, mammalian cells and several yeasts and fungi [1][2][3]. Production processes had to be developed that employ platforms which meet both, the demand for efficient mass production and criteria of safety and authenticity of the produced compounds. In this respect yeasts offer considerable advantages over alternative microbial and mammalian cell systems in providing low-cost screening and production systems for authentically processed and modified proteins. The organisms meet safety prerequisites in that they do not harbour pyrogens, pathogens or viral inclusions [4,5]. Recent engineering of yeast hosts with

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Section: H Polymorpha -Based Processes Under Control Of mentioning

confidence: 99%

Section: H Polymorpha -Based Processes Under Control Of mentioning

confidence: 99%

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

Section: Culturing Of Arxula Adeninivorans Strainsmentioning

confidence: 99%

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Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment

et al. 2009

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Glucose‐induced production of recombinant proteins in Hansenulapolymorpha mutants deficient in catabolite repression

Krasovska

Stasyk

Nahorny

et al. 2007

Biotech & Bioengineering

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The most commonly used expression platform for production of recombinant proteins in the methylotrophic yeast Hansenula polymorpha relies on the strong and strictly regulated promoter from the gene encoding peroxisomal enzyme alcohol (or methanol) oxidase (P(MOX)). Expression from P(MOX) is induced by methanol and is partially derepressed in glycerol or xylose medium, whereas in the presence of hexoses, disaccharides or ethanol, it is repressed. The need for methanol for maximal induction of gene expression in large-scale fermentation is a significant drawback, as this compound is toxic, flammable, supports a slow growth rate and requires extensive aeration. We isolated H. polymorpha mutants deficient in glucose repression of P(MOX) due to an impaired HpGCR1 gene, and other yet unidentified secondary mutations. The mutants exhibited pronounced defects in P(MOX) regulation only by hexoses and xylose, but not by disaccharides or ethanol. With one of these mutant strains as hosts, we developed a modified two-carbon source mode expression platform that utilizes convenient sugar substrates for growth (sucrose) and induction of recombinant protein expression (glucose or xylose). We demonstrate efficient regulatable by sugar carbon sources expression of three recombinant proteins: a secreted glucose oxidase from the fungus Aspergillus niger, a secreted mini pro-insulin, and an intracellular hepatitis B virus surface antigen in these mutant hosts. The modified expression platform preserves the favorable regulatable nature of P(MOX) without methanol, making a convenient alternative to the traditional system.

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Investigation into struvite precipitation: A commonly encountered problem during fermentations on chemically defined media

Steimann,

Wollborn,

Röck

et al. 2023

Biotech & Bioengineering

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Chemically defined mineral media are widely used in bioprocesses, as these show less batch to batch variation compared with complex media. Nonetheless, the recommended media formulations often lead to the formation of precipitants at elevated pH values. These precipitates are insoluble and reduce the availability of macronutrients to the cells, which can result in limiting growth rates and lower productivity. They can also damage equipment by clogging pipes, hoses, and spargers in stirred tank fermenters. In this study, the observed precipitate was analyzed via X‐ray fluorescence spectroscopy and identified as the magnesium ammonium phosphate salt struvite (MgNH4PO4 × 6H2O). The solubility of struvite crystals is known to be extremely low, causing the macronutrients magnesium, phosphate, and ammonium to be bound in the struvite crystals. Here, it was shown that struvite precipitates can be redissolved under common fermentation conditions. Furthermore, it was found that the struvite particle size distribution has a significant effect on the dissolution kinetics, which directly affects macronutrient availability. At a certain particle size, struvite crystals rapidly dissolved and provided unlimiting growth conditions. Therefore, struvite formation should be considered during media and bioprocess development, to ensure that the dissolution kinetics of struvite are faster than the growth kinetics.

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Comparative Fermentation

Cited by 12 publications

References 0 publications

Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment

Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment

Glucose‐induced production of recombinant proteins in Hansenulapolymorpha mutants deficient in catabolite repression

Investigation into struvite precipitation: A commonly encountered problem during fermentations on chemically defined media

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