Recent progress of the research on novel microbial metabolites

Three kinds of microbial metabolites with unique structures and activities were discovered in cell-based screening systems. Lactacystin with a peptide-like structure, isolated as an inducer of neurite outgrowth of Neuro 2a cells (a mouse neuroblastoma cell line), was found to inhibit proteasome functions specifically by binding to the active site N-terminal threonine of the catalytic subunit. Macrospelides with a 16-membered-ring structure embodying three lactone likages were isolated as inhibitors of the adhesion of HL-60 cells to the monolayer of LPS-activated human umbilical vein endothelial cells. They blocked the cell-cell adhesion by inhibiting the endothelial cell-leukocyte adhesion molecule-1/sialyl-Lewis(X) recognition system. Macrosphelides proved effective in in vivo models of the lung metastasis and fibrosis. Madindolines with an indoline-diketocyclopenetene connecting structure, isolated as inhibitors of the growth of IL-6 dependent cells, were found to inhibit IL-6 and IL-11 functions selectively.