Glucose‐induced production of recombinant proteins in <i>Hansenula</i><i>polymorpha</i> mutants deficient in catabolite repression

Krasovska, Olena S.; Stasyk, Olena G.; Nahorny, Viktor O.; Granovski, Nikolai; Кордюм, В. А.; Vozianov, Oleksandr F.; Sibirny, Andriy А.

doi:10.1002/bit.21284

Cited by 29 publications

(17 citation statements)

References 42 publications

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“…Such modified promoters (e.g. P MOX in H. polymorpha and P AOX1 in P. pastoris ) are no longer methanol inducible, showing in most cases either an inducible phenotype from molecules other than methanol, or a more pronounced derepressed phenotype [134,135]. …”

Section: Introductionmentioning

confidence: 99%

Carbon source dependent promoters in yeasts

et al. 2014

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Budding yeasts are important expression hosts for the production of recombinant proteins.The choice of the right promoter is a crucial point for efficient gene expression, as most regulations take place at the transcriptional level. A wide and constantly increasing range of inducible, derepressed and constitutive promoters have been applied for gene expression in yeasts in the past; their different behaviours were a reflection of the different needs of individual processes.Within this review we summarize the majority of the large available set of carbon source dependent promoters for protein expression in yeasts, either induced or derepressed by the particular carbon source provided. We examined the most common derepressed promoters for Saccharomyces cerevisiae and other yeasts, and described carbon source inducible promoters and promoters induced by non-sugar carbon sources. A special focus is given to promoters that are activated as soon as glucose is depleted, since such promoters can be very effective and offer an uncomplicated and scalable cultivation procedure.

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Section: Introductionmentioning

confidence: 99%

Carbon source dependent promoters in yeasts

et al. 2014

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“…Knowledge of the molecular mechanisms of catabolite regulation in H. polymorpha is of basic and practical interest. Mutants with altered catabolite regulation of the AO gene promoter may be promising hosts for the expression of recombinant proteins in methanol‐free media (Krasovska et al , 2007), and protein products can be targetted to peroxisomes applying this organelle as a storage vesicle (van Dijk et al , 2000). The availability of the full H. polymorpha genome sequence (Ramezani‐Rad et al , 2003) made it possible to search for orthologues of S. cerevisiae genes involved in catabolite repression and to study their function.…”

Section: Introductionmentioning

confidence: 99%

The role ofHansenula polymorpha MIG1homologues in catabolite repression and pexophagy

Stasyk

Zutphen

Kang

et al. 2007

FEMS Yeast Research

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In the methanol-utilizing yeast Hansenula polymorpha, glucose and ethanol trigger the repression of peroxisomal enzymes at the transcriptional level, and rapid and selective degradation of methanol-induced peroxisomes by means of a process termed pexophagy. In this report we demonstrate that deficiency in the putative H. polymorpha homologues of transcriptional repressors Mig1 (HpMig1 and HpMig2), as well as HpTup1, partially and differentially affects the repression of peroxisomal alcohol oxidase by sugars and ethanol. As reported earlier, deficiency in HpTup1 leads to impairment of glucose- or ethanol-induced macropexophagy. In H. polymorpha mig1mig2 double-deletion cells, macropexophagy was also substantially impaired, whereas micropexophagy became a dominant mode of autophagic degradation. Our findings suggest that homologues of the elements of the Saccharomyces cerevisiae main repression pathway have pleiotropic functions in H. polymorpha.

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“…Also, H. polymropha is a biotechnologically important yeast known as an efficient expression platform for heterologous proteins, governed mostly by glucose-repressible promoters (14,21). In addition, this thermotolerant yeast has recently been suggested as a promising organism for hightemperature fermentation of major sugars of lignocellulose hydrolysates, glucose and xylose (38).…”

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Identification of Hexose Transporter-Like Sensor HXS1 and Functional Hexose Transporter HXT1 in the Methylotrophic Yeast Hansenula polymorpha

et al. 2008

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We identified in the methylotrophic yeast Hansenula polymorpha (syn. Pichia angusta) a novel hexose transporter homologue gene, HXS1 (hexose sensor), involved in transcriptional regulation in response to hexoses, and a regular hexose carrier gene, HXT1 (hexose transporter). The Hxs1 protein exhibits the highest degree of primary sequence similarity to the Saccharomyces cerevisiae transporter-like glucose sensors, Snf3 and Rgt2. When heterologously overexpressed in an S. cerevisiae hexose transporter-less mutant, Hxt1, but not Hxs1, restores growth on glucose or fructose, suggesting that Hxs1 is nonfunctional as a carrier. In its native host, HXS1 is expressed at moderately low level and is required for glucose induction of the H. polymorpha functional low-affinity glucose transporter Hxt1. Similarly to other yeast sensors, one conserved amino acid substitution in the Hxs1 sequence (R203K) converts the protein into a constitutively signaling form and the C-terminal region of Hxs1 is essential for its function in hexose sensing. Hxs1 is not required for glucose repression or catabolite inactivation that involves autophagic degradation of peroxisomes. However, HXS1 deficiency leads to significantly impaired transient transcriptional repression in response to fructose, probably due to the stronger defect in transport of this hexose in the hxs1⌬ deletion strain. Our combined results suggest that in the Crabtree-negative yeast H. polymorpha, the single transporter-like sensor Hxs1 mediates signaling in the hexose induction pathway, whereas the rate of hexose uptake affects the strength of catabolite repression.As a favorite carbon substrate, glucose exerts numerous strong and well-coordinated effects on the physiological state of yeast cells. They include gene-specific regulation of transcription and mRNA stability as well as regulation at the posttranslational level: e.g., catabolite inactivation of certain glucoserepressible enzymes (3,13,19). Signaling pathways involved in different glucose effects have been studied mostly in the model yeast Saccharomyces cerevisiae. A number of participating components have been identified, and some have been shown to have conserved functions in other yeast species (for review, see references 12, 36, and 41). Nevertheless, knowledge of glucose-triggered regulatory pathways for Crabtree-negative yeasts (which contrary to S. cerevisiae, are unable to produce ethanol aerobically in the presence of high external glucose concentrations) (11) that primarily rely on respiratory metabolism still remains very limited. In particular, the first stages, how glucose is sensed, and the molecular triggers involved in different pathways are the least understood aspects of these yeast species.Two nontransporting glucose carrier homologues, Snf3 and Rgt2, have been shown to function as glucose sensors in S. cerevisiae in a pathway of transcriptional induction. They differentially regulate expression of the functional hexose transporters in response to extracellular glucose concentration (32). This ...

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

Cited by 29 publications

References 42 publications

Carbon source dependent promoters in yeasts

Carbon source dependent promoters in yeasts

The role ofHansenula polymorpha MIG1homologues in catabolite repression and pexophagy

Identification of Hexose Transporter-Like Sensor HXS1 and Functional Hexose Transporter HXT1 in the Methylotrophic Yeast Hansenula polymorpha

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