Efficient protein production by yeast requires global tuning of metabolism

Huang, Mingtao,1984Chalmers tekniska högskola,Chalmers University of Technology (författare)

QC 20180508
The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular, altered energy metabolism resulting in reduced respiration and increased fermentation, as well as balancing of amino-acid biosynthesis and reduced thiamine biosynthesis seem to be particularly important. We confirm our findings by inverse engineering and physiological characterization and show that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion.

MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
amylase
carbohydrate
protein
thiamine
biological production
biotechnology
efficiency measurement
genetic engineering
metabolism
yeast
AAC3 gene
amino acid synthesis
amylase release
ANB1 gene
Article
bacterium culture
carbohydrate metabolism
CYC7 gene
DAN1 gene
endoplasmic reticulum stress
energy metabolism
fermentation
fungal gene
FUR1 gene
genome-wide association study
MSS11 gene
nonhuman
PHO12 gene
PHO84 gene
PHO89 gene
protein metabolism
protein secretion
reporter gene
RNA sequence
SNF2 gene
SPL2 gene
SUT1 gene
SWI4 gene
TEC1 gene
TIR3 gene

Bao, Jichen,1988Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)jichen (författare)
Hallström, Björn M.KTH,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)(Swepub:kth)u1ih19oh (författare)
Petranovic Nielsen, Dina,1975Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)dinap (författare)
Nielsen, JensKTH,Science for Life Laboratory, SciLifeLab,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (författare)
Chalmers tekniska högskolaScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Av författaren/redakt...: Huang, Mingtao, ...; Bao, Jichen, 198 ...; Hallström, Björn ...; Petranovic Niels ...; Nielsen, Jens

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