Lee Ha-Yeon, Kwun Se-Young, Park Eun-Hee, Yoon Jeong-Ah, Kim Myoung-Dong
Department of Food Biotechnology and Environmental Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Agro-Food Research Institute, Gangwon State Agricultural Research & Extension Services, Chuncheon 24203, Republic of Korea.
J Microbiol Biotechnol. 2025 Jul 14;35:e2502001. doi: 10.4014/jmb.2502.02001.
Protein tyrosine phosphatase 1B (PTP1B) removes phosphate groups from phosphorylated tyrosine proteins in human cells, particularly in the insulin and leptin signaling pathways. It is a key drug target for ailments such as type 2 diabetes and obesity. However, there is a lack of highly specific PTP1B inhibitor drugs. This study employed recombinant that co-expressed PTP1B and v-Src (viral sarcoma protein tyrosine kinase) to screen for novel PTP1B inhibitors derived from actinomycete extracts. Eight extracts significantly suppressed the growth of the recombinant by inhibiting PTP1B expression, indicating their potential as PTP1B inhibitors. In a protein-chip assay, actinomycete extract 4585DW showed PTP1B inhibitory activity comparable to the positive controls, suramin and vanadate. The extract was non-cytotoxic in mammalian and yeast cells and inhibited PTP1B with m and max values of 10.91 ± 0.50 mM and 0.02 ± 0.00 μmol/min, respectively. In conclusion, 4585DW is a promising candidate for further investigation as a PTP1B inhibitor.
蛋白酪氨酸磷酸酶1B（PTP1B）可去除人体细胞中磷酸化酪氨酸蛋白上的磷酸基团，尤其是在胰岛素和瘦素信号通路中。它是2型糖尿病和肥胖症等疾病的关键药物靶点。然而，目前缺乏高度特异性的PTP1B抑制剂药物。本研究利用共表达PTP1B和v-Src（病毒肉瘤蛋白酪氨酸激酶）的重组体来筛选源自放线菌提取物的新型PTP1B抑制剂。八种提取物通过抑制PTP1B表达显著抑制了重组体的生长，表明它们具有作为PTP1B抑制剂的潜力。在蛋白质芯片检测中，放线菌提取物4585DW显示出与阳性对照苏拉明和钒酸盐相当的PTP1B抑制活性。该提取物在哺乳动物细胞和酵母细胞中无细胞毒性，抑制PTP1B的米氏常数（Km）和最大反应速度（Vmax）值分别为10.91±0.50 mM和0.02±0.00 μmol/min。总之，4585DW作为一种PTP1B抑制剂具有进一步研究的潜力。
