Tyrosinase, a type I
membrane glycoprotein, is synthesized and glycosylated in the endoplasmic reticulum (ER) and Golgi. The
enzyme is subsequently transported to melanosomes where it participates in melanogenesis. Previous studies showed that the disruption of early ER N-
glycan processing by deoxynojirimycin (DNJ), an inhibitor of
alpha-glucosidase, suppresses
tyrosinase enzymatic activity and melanogenesis. However, the disruption of late
glycan processing, mainly performed by ER and Golgi alpha-1,2-mannosidases, on
tyrosinase enzymatic activity and melanogenesis remains to be investigated. Following treatment of HM3KO human
melanoma cells with deoxymannojirimycin (
DMJ), an inhibitor of alpha-1,2-mannosidase, transport of
tyrosinase to the melanosome, enzymatic activity, and melanogenesis were reduced in a dose-dependent manner. However, DMJ did not directly inhibit
tyrosinase enzymatic activity and expression. Interestingly, an extract of Streptomyces subrutilus culture medium (ESSCM) containing DMJ and DNJ as the main components inhibited glycosylation and transport of
tyrosinase to the melanosome as well as
melanin synthesis, but with no negative effects on cell viability. These inhibitory effects of ESSCM were stronger than those of DMJ or DNJ alone.
Tyrosinase glycosylation and melanogenesis in HM3KO
melanoma cells were more effectively inhibited by DMJ and DNJ combined than DMJ or DNJ alone. Accordingly, we propose that ESSCM is a potential candidate for treating undesirable
hyperpigmentation conditions, such as
melasma, postinflammatory melanoderma, and solar
lentigo.