Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00543022" target="_blank" >RIV/61388963:_____/21:00543022 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22330/21:43922711

Result on the web

<a href="https://doi.org/10.1007/s00253-021-11336-5" target="_blank" >https://doi.org/10.1007/s00253-021-11336-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00253-021-11336-5" target="_blank" >10.1007/s00253-021-11336-5</a>

Result language

angličtina

Original language name

Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins

Original language description

Folding and processing of proteins in the endoplasmic reticulum (ER) are major impediments in the production and secretion of proteins from Pichia pastoris (Komagataella sp.). Overexpression of recombinant genes can overwhelm the innate secretory machinery of the P. pastoris cell, and incorrectly folded proteins may accumulate inside the ER. To restore proper protein folding, the cell naturally triggers an unfolded protein response (UPR) pathway, which upregulates the expression of genes coding for chaperones and other folding-assisting proteins (e.g., Kar2p, Pdi1, Ero1p) via the transcription activator Hac1p. Unfolded/misfolded proteins that cannot be repaired are degraded via the ER-associated degradation (ERAD) pathway, which decreases productivity. Co-expression of selected UPR genes, along with the recombinant gene of interest, is a common approach to enhance the production of properly folded, secreted proteins. Such an approach, however, is not always successful and sometimes, protein productivity decreases because of an unbalanced UPR. This review summarizes successful chaperone co-expression strategies in P. pastoris that are specifically related to overproduction of foreign proteins and the UPR. In addition, it illustrates possible negative effects on the cell’s physiology and productivity resulting from genetic engineering of the UPR pathway. We have focused on Pichia’s potential for commercial production of valuable proteins and we aim to optimize molecular designs so that production strains can be tailored to suit a specific heterologous product.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Applied Microbiology and Biotechnology

ISSN

0175-7598

e-ISSN

1432-0614

Volume of the periodical

105

Issue of the periodical within the volume

11

Country of publishing house

DE - GERMANY

Number of pages

18

Pages from-to

4397-4414

UT code for WoS article

000654865100001

EID of the result in the Scopus database

2-s2.0-85106484238