Inhibition of Lipid‐Linked Mannose and Mannoprotein Synthesis in Yeast by Diumycin in vitro

Diumycin, a phosphoglycolipid antibiotic, inhibits different mannosyl transfer reactions in yeast. Using membrane preparations, the drug effectively inhibited the formation of dolichyl phosphate mannose (DolP‐Man); 50% inhibition was observed at approximately 10 μg/ml. To a lesser extent also mannosyl transfer from DolP‐Man to protein decreased in presence of diumycin. Both mannosyl transfer to protein‐serine/threonine acceptor sites as well as into positions within the asparagine‐linked polymannose part of the yeast mannoprotein are inhibited to about 60% under conditions where DolP‐Man formation is blocked. DolP‐Man synthesis as well as mannosyl transfer from DolP‐Man to protein are also inhibited by diumycin using solubilized enzymes and exogenous acceptor substrates. Glycosyltransfer reactions from GDP‐mannose either to protein‐serine/threonine‐linked mannose (formation of short manno‐oligosaccharides) or to dolichyl‐diphosphate‐linked chitobiose (formation of lipid‐linked trisaccharide) are not inhibited by diumycin under conditions where DolP‐Man synthesis is blocked by the antibiotic. The inhibitory action of diumycin on DolP‐Man formation does not seem to be competitive with respect to dolichyl phosphate, since it cannot be overcome by higher concentrations of dolichyl phosphate.