In this study,a Streptomyces sp. 89-2-2 isolated from Lop Nur Salt Lake in Xinjiang was identified by multiphase classification.Effects of the strain ethyl acetate extract on mouse melanoma B16 cell proliferation,tyrosinase activity and melanin content were determined by CCK-8 assay,L-Dopa oxidation method and NaOH dissolution method.Taken the inhibitory activity on tyrosinase as evaluation index,we detected the differential metabolites produced by Streptomyces sp. 89-2-2 under the two fermentation conditions of before and after optimization by liquid chromatograph-mass spectrometer.The aim of this study was to analyze the types of metabolites that may have inhibitory activity.The strain was preliminary identified as Streptomyces setonii 89-2-2.The ethyl acetate extract of S. setonii 89-2-2 had little cytotoxic,but could effectively inhibit the tyrosinase activity and melanogenesis in the B16 cells under the concentration of 100-1 000 μg/ml.The above results were significantly different from those of the blank groups (P < 0.05).Metabolomics test results showed that the differential metabolites produced by S. setonii 89-2-2 were mainly vitamins,aromatic compounds and carboxylic acids.This study provides an important scientific basis for the development of tyrosinase inhibitors and melanin synthesis inhibitors from Streptomycesof Lop Nur in Xinjiang.