Efficient protein production by yeast requires global tuning of metabolism

• 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.

Ämnesord

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)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)