Cystine import is a valuable but risky process whose hazards Escherichia coli minimizes by inducing a cysteine exporter

• Published in: Molecular microbiology 2020-01, Vol.113 (1), p.22-39
• Main Authors: Korshunov, Sergey, Imlay, Karin R. Chonoles, Imlay, James A.
• Format: Article
• Language: English
• Subjects: Amino Acid Transport Systems, Neutral - metabolism; Amino acids; Cysteine; Cystine; Cystine - metabolism; Disulfide bonds; E coli; Escherichia coli; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Imports; Incompatibility; Isoleucine; Leucine-Responsive Regulatory Protein - metabolism; NADP; Oxidation; Oxidation-Reduction; Oxygen; Product inhibition; Protein transport; Proteins; Reactive oxygen species; Sulfides; Sulfur
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.14403

Summary 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. When E. coli encounters environmental cystine, it rapidly imports it, reduces it to cysteine and then exports most of the cysteine. This odd behavior is ultimately an awkward way to minimize the disulfide stress that results from the import of cystine.