Discovery of\nSporachelins by Genome Mining of a <i>Micromonospora</i> Strain

Myxochelins\nare a group of catecholate siderophores encoded\nby\n <i>mxc</i> biosynthetic gene clusters (BGCs). They are\nmainly produced by myxobacteria and display a wide variety of bioactivities.\nHerein, we report a group of new myxochelins produced not by a myxobacterial\nstrain but by an actinobacteria strain, <i>Micromonospora</i> sp. TMD166. They consisted of six new compounds, designated as sporachelins\nA (<b>1</b>), A1 (<b>2</b>), B (<b>3</b>), C (<b>4</b>), D (<b>5</b>), and E (<b>6</b>), and the known\ncompound myxochelin A (<b>7</b>). The planar structures were\ndetermined by comprehensive analyses of 1D and 2D NMR spectroscopic\ndata, and the absolute configurations were confirmed by Marfey’s\nanalysis and chemical synthesis. The six sporachelins are the first\nexamples of acylated derivatives at the primary alcohol of myxochelin\nA. These molecules were found to inhibit human 5-lipoxygenase. In\naddition, <b>1</b>–<b>7</b> exhibited antifibrotic\nactivity in the TGFβ1-induced human hepatic cell line LX-2 by\nsuppressing fibrosis-related genes <i>COL1A1</i>, <i>ACTA2</i>, and <i>TGFB1</i> expression. This is the\nfirst report of antifibrotic activity by myxochelins.