Fungal metabolite sulfamisterin suppresses sphingolipid synthesis through inhibition of serine palmitoyltransferase.

摘要: Sphingolipids and their metabolites are known to modulate various cellular events including proliferation, differentiation, apoptosis. Serine palmitoyltransferase (SPT) is the enzyme that catalyzes first step of biosynthesis all sphingolipids. Here, we report a newly identified antibiotic, sulfamisterin, derived from fungus Pycnidiella sp., specific inhibitor SPT. The chemical structure sulfamisterin resembles both sphingosine as well potent SPT, ISP-1 (myriocin). Sulfamisterin inhibited SPT activity with IC(50) = 3 nM in cell-free lysate prepared Chinese hamster ovary (CHO) fibroblasts. markedly sphingolipids living CHO cells yeast Saccharomyces cerevisiae monitored by radioactive precursors. Unlike experiments, 10 microM was required for complete inhibition sphingolipid intact cells. We also synthesized series structural analogues examined activities cell systems.