The C orynebacterium glutamicum mycothiol peroxidase is a reactive oxygen species‐scavenging enzyme that shows promiscuity in thiol redox control

Cysteine glutathione peroxidases ( CysGPxs ) control oxidative stress levels by reducing hydroperoxides at the expense of cysteine thiol (‐ SH ) oxidation, and the recovery of their peroxidatic activity is generally accomplished by thioredoxin ( T rx). C orynebacterium glutamicum mycothiol peroxidase ( M px) is a member of the CysGPx family. We discovered that its recycling is controlled by both the Trx and the mycothiol ( MSH ) pathway. After H 2 O 2 reduction, a sulfenic acid (‐ SOH ) is formed on the peroxidatic cysteine ( Cys36 ), which then reacts with the resolving cysteine ( Cys79 ), forming an intramolecular disulfide ( S ‐ S ), which is reduced by Trx . Alternatively, the sulfenic acid reacts with MSH and forms a mixed disulfide. Mycoredoxin 1 ( Mrx1 ) reduces the mixed disulfide, in which M rx1 acts in combination with MSH and mycothiol disulfide reductase as a biological relevant monothiol reducing system. Remarkably, Trx can also take over the role of Mrx1 and reduce the Mpx‐MSH mixed disulfide using a dithiol mechanism. Furthermore, Mpx is important for cellular survival under H 2 O 2 stress, and its gene expression is clearly induced upon H 2 O 2 challenge. These findings add a new dimension to the redox control and the functioning of CysGPx s in general.