Bozeman, Montana – October 1, 2026 A groundbreaking discovery by Montana State University’s (MSU) scientists has unveiled a hitherto unknown cellular survival pathway that allows mammalian cells to produce cysteine, a crucial amino acid, even when primary disulfide reductase systems fail. The revelation, published in Nature Chemical Biology, emerged from a nine-year study that began in 2014 when genetically engineered mice lacking known cystine-to-cysteine conversion mechanisms survived under conditions that should have been fatal.
The discovery challenges decades-old beliefs that cells could not obtain cysteine externally and must generate it internally by breaking down cystine via disulfide reductase systems, with at least one functioning system considered essential for life. Led by Ed Schmidt, a professor of genetics and development in MSU’s Department of Microbiology and Cell Biology, the team identified an alternative chemical route: when the main disulfide reductase pathway is unavailable, mammalian cells break an adjacent carbon-sulfur bond in cystine to free cysteine.
Collaborator Peter Nagy and his group at the Hungarian National Institute of Oncology in Budapest provided analytical capabilities that helped confirm this backup mechanism. Schmidt suggests the pathway may have evolved as an ancient defense against electrophilic toxins, giving early multicellular organisms an evolutionary advantage. However, the same mechanism that protects healthy cells could also help cancer cells survive chemotherapy, radiation, or immunotherapy by defending against treatment-induced stress.
Researchers now aim to selectively interfere with this pathway in tumors to make cancers more vulnerable to existing therapies. The study involved multiple MSU students, including undergraduate co-first authors Zoe Seaford and Sydney Austad, undergraduate participants Martina Serrano Alvarez and Reed Noyd, and doctoral student Colin Miller.
No specific funding amounts, market impacts, stock prices, or financial figures were disclosed in the source material. Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the formula HS−CH2−CH(NH2)−COOH. The thiol side chain in cysteine enables the formation of disulfide bonds, and often participates in enzymatic reactions as a nucleophile.
Cysteine is chiral, but both D- and L-cysteine are found in nature. L-Cysteine is a protein monomer in all biota, and D-cysteine acts as a signaling molecule in mammalian nervous systems. Cysteine is named after its discovery in urine, which comes from the urinary bladder or cyst, from Greek κύστις kýstis, “bladder”.
The thiol is susceptible to oxidation to give the disulfide derivative cystine, which serves an important structural role in many proteins. In this case, the symbol Cyx is sometimes used.
The deprotonated form can generally be described by the symbol Cym as well. When used as a food additive, cysteine has the E number E920. Cysteine is encoded by the codons UGU and UGC.
In animals, biosynthesis begins with the amino acid serine. The sulfur is derived from methionine, which is converted to homocysteine through the intermediate S-adenosylmethionine.
Cystathionine beta-synthase then combines homocysteine and serine to form the asymmetrical thioether cystathionine. The enzyme cystathionine gamma-lyase converts the cystathionine into cysteine and alpha-ketobutyrate. This pathway is called the transsulfuration pathway.
In plants, the biosynthesis of cysteine is more complex and involves multiple steps, including the conversion of methionine to O-acetylserine by O-acetylserine (thiol) lyase, and then to cysteine by serine acetyltransferase and cysteine synthase. Plants also have the ability to take up cysteine from the soil through their roots. Dietary sources of cysteine include poultry, eggs, beef, and whole grains.
In high-protein diets, cysteine may be partially responsible for reduced blood pressure and stroke risk. Although classified as a nonessential amino acid, in rare cases, cysteine may be essential for infants, the elderly, and individuals with certain metabolic diseases or who suffer from malabsorption syndromes.
