A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation

Ero1 and Pdi1 are essential elements of the pathway for the formation of di sulphide bonds within the endoplasmic reticulum (ER). By screening for alte rnative oxidation pathways in Saccharomyces cerevisiae, we identified EM as a gene that when overexpressed can restore viability and disulphide bond f ormation to an ero1-1 mutant strain. EM encodes a luminal ER protein of rel ative molecular mass 22,000. Purified recombinant Erv2p is a flavoenzyme th at can catalyse O-2-dependent formation of disulphide bonds. Erv2p transfer s oxidizing equivalents to Pdi1p by a dithiol-disulphide exchange reaction, indicating that the Erv2p-dependent pathway for disulphide bond formation closely parallels that of the previously identified Ero1p-dependent pathway .