TY - JOUR
T1 - Cystine import is a valuable but risky process whose hazards Escherichia coli minimizes by inducing a cysteine exporter
AU - Korshunov, Sergey
AU - Imlay, Karin R.Chonoles
AU - Imlay, James A.
N1 - Funding Information:
We are grateful to Stefano Mancini for his assistance with the RNA seq analysis. We thank Jon Beckwith and his laboratory for generously providing key strains. This study was funded by grant GM101012 from the National Institutes of Health.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2020/1/1
Y1 - 2020/1/1
N2 - The structure of free cysteine makes it vulnerable to oxidation by molecular oxygen; consequently, organisms that live in oxic habitats have acquired the ability to import cystine as a sulfur source. We show that cystine imported into Escherichia coli can transfer disulfide bonds to cytoplasmic proteins. To minimize this problem, the imported cystine is rapidly reduced. However, this conversion of cystine to cysteine precludes product inhibition of the importer, so cystine import continues into cells that are already sated with cysteine. The burgeoning cysteine pool is itself hazardous, as cysteine promotes the formation of reactive oxygen species, triggers sulfide production and competitively inhibits a key enzyme in the isoleucine biosynthetic pathway. The Lrp transcription factor senses the excess cysteine and induces AlaE, an export protein that pumps cysteine back out of the cell until transcriptional controls succeed in lowering the amount of the importer. While it lasts, the overall phenomenon roughly doubles the NADPH demand of the cell. It comprises another example of the incompatibility of the reduced cytoplasms of microbes with the oxic world in which they dwell. It also reveals one natural source of cytoplasmic disulfide stress and sheds light on a role for broad-spectrum amino acid exporters.
AB - The structure of free cysteine makes it vulnerable to oxidation by molecular oxygen; consequently, organisms that live in oxic habitats have acquired the ability to import cystine as a sulfur source. We show that cystine imported into Escherichia coli can transfer disulfide bonds to cytoplasmic proteins. To minimize this problem, the imported cystine is rapidly reduced. However, this conversion of cystine to cysteine precludes product inhibition of the importer, so cystine import continues into cells that are already sated with cysteine. The burgeoning cysteine pool is itself hazardous, as cysteine promotes the formation of reactive oxygen species, triggers sulfide production and competitively inhibits a key enzyme in the isoleucine biosynthetic pathway. The Lrp transcription factor senses the excess cysteine and induces AlaE, an export protein that pumps cysteine back out of the cell until transcriptional controls succeed in lowering the amount of the importer. While it lasts, the overall phenomenon roughly doubles the NADPH demand of the cell. It comprises another example of the incompatibility of the reduced cytoplasms of microbes with the oxic world in which they dwell. It also reveals one natural source of cytoplasmic disulfide stress and sheds light on a role for broad-spectrum amino acid exporters.
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U2 - 10.1111/mmi.14403
DO - 10.1111/mmi.14403
M3 - Article
C2 - 31612555
AN - SCOPUS:85074970776
SN - 0950-382X
VL - 113
SP - 22
EP - 39
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 1
ER -