Production of IFNα-2a in Hansenula polymorpha

Müller, Florian; Tieke, Anni; Waschk, Dorothea; Mühle, Christine; Seigelchifer, Mauricio; Pesce, Analia; Jenzelewski, Volker; Gellissen, Gerd

doi:10.1016/s0032-9592(02)00037-7

Cited by 24 publications

(7 citation statements)

References 29 publications

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“…H. polymorpha is capable of growing across a relatively broad pH range (3.0-7.0). Different pH values were found to be optimal from the point of view of a recombinant protein's stability: pH 6.0 was optimal in the production of recombinant human epidermal factor (Moon et al 2002) and human serum albumin (Kang et al 2001), and pH 2.8 was optimal in the production of IFNα-2a (Muller et al 2002). The rational reasons for that are either an improved productivity or stability of the product (Shi et al 2003) or decreased proteolysis (Jahic et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Chen

Wang

et al. 2008

Appl Microbiol Biotechnol

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Uricase is an important medical enzyme which can be used to determine urate in clinical analysis, to therapy gout, hyperuricemia, and tumor lysis syndrome. Uricase of Candida utilis was successfully expressed in Hansenula polymorpha under the control of methanol oxidase promoter using Saccharomyces cerevisiae α-factor signal peptide as the secretory sequence. Recombinant H. polymorpha MU200 with the highest extracellular uricase production was characterized with three copies of expression cassette and selected for process optimization for the production of recombinant enzyme. Among the parameters investigated in shaking flask cultures, the pH value of medium and inoculum size had great influence on the recombinant uricase production. The maximum extracellular uricase yield of 2.6 U/ml was obtained in shaking flask culture. The yield of recombinant uricase was significantly improved by the combined use of a high cell-density cultivation technique and a pH control strategy of switching culture pH from 5.5 to 6.5 in the induction phase. After induction for 58 h, the production of recombinant uricase reached 52.3 U/ml (about 2.1 g/l of protein) extracellularly and 60.3 U/ml (about 2.4 g/l) intracellularly in fed-batch fermentation, which are much higher than those expressed in other expression systems. To our knowledge, this is the first report about the heterologous expression of uricase in H. polymorpha.

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Section: Discussionmentioning

confidence: 99%

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Chen

Wang

et al. 2008

Appl Microbiol Biotechnol

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“…Yield was calculated from titer and carbon source consumption based on reported feed rates and durations. Values are based on data from CHO (Huang et al, ; Keen & Rapson, ), P. pastoris (Mallem et al, ; Potgieter et al, ; Werten, Van Den Bosch, Wind, Mooibroek, & De Wolf, ), H. polymorpha (Mayer et al, ; Müller et al, ), T. reesei (Landowski et al, ; Ma et al, ; Nyyssönen et al, ), and A. oryzae (Ward et al, ). With further development, alternative hosts could also see the order‐of‐magnitude improvement in fermentation performance that has been achieved in CHO.…”

Section: Fermentation Performancementioning

confidence: 99%

Reexamining opportunities for therapeutic protein production in eukaryotic microorganisms

Wright

Kuo

Colant

et al. 2017

Biotech & Bioengineering

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Antibodies are an important class of therapeutics and are predominantly produced in Chinese Hamster Ovary (CHO) cell lines. While this manufacturing platform is sufficiently productive to supply patient populations of currently approved therapies, it is unclear whether or not the current CHO platform can address two significant areas of need: affordable access to biologics for patients around the globe and production of unprecedented quantities needed for very large populations of patients. Novel approaches to recombinant protein production for therapeutic biologic products may be needed, and might be enabled by non-mammalian expression systems and recent advances in bioengineering. Eukaryotic microorganisms such as fungi, microalgae, and protozoa offer the potential to produce high-quality antibodies in large quantities. In this review, we lay out the current understanding of a wide range of species and evaluate based on theoretical considerations which are best poised to deliver a step change in cost of manufacturing and volumetric productivity within the next decade.Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26383/full.

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“…In other examples, overexpression of secretory pathway genes has been shown to improve both, the yield and the quality of a recombinant product in several yeast platforms. Examples include the overexpression of KAR2 [53], PDI [54], SSO1/2 [55], CMK2 [56] and KEX2 [57]. However, it became apparent that the observed improvements were restricted to a specific recombinant product development in meeting the demands to overcome a particular limitation in the respective recombinant strains.…”

Section: Resultsmentioning

confidence: 99%

Application of a wide-range yeast vector (CoMed™) system to recombinant protein production in dimorphic Arxula adeninivorans, methylotrophic Hansenula polymorpha and other yeasts

et al. 2006

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Background: Yeasts provide attractive expression platforms in combining ease of genetic manipulation and fermentation of a microbial organism with the capability to secrete and to modify proteins according to a general eukaryotic scheme. However, early restriction to a single yeast platform can result in costly and time-consuming failures. It is therefore advisable to assess several selected systems in parallel for the capability to produce a particular protein in desired amounts and quality. A suitable vector must contain a targeting sequence, a promoter element and a selection marker that function in all selected organisms. These criteria are fulfilled by a wide-range integrative yeast expression vector (CoMed™) system based on A. adeninivorans-and H. polymorpha-derived elements that can be introduced in a modular way.

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Production of IFNα-2a in Hansenula polymorpha

Cited by 24 publications

References 29 publications

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene

Reexamining opportunities for therapeutic protein production in eukaryotic microorganisms

Application of a wide-range yeast vector (CoMed™) system to recombinant protein production in dimorphic Arxula adeninivorans, methylotrophic Hansenula polymorpha and other yeasts

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