Discovery of Sporachelins by Genome Mining of a Micromonospora Strain

Myxochelins are a group of catecholate siderophores encoded by mxc biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, Micromonospora sp. TMD166. They consisted of six new compounds, designated as sporachelins A (1), A1 (2), B (3), C (4), D (5), and E (6), and the known compound myxochelin A (7). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, 1-7 exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes COL1A1, ACTA2, and TGFB1 expression. This is the first report of antifibrotic activity by myxochelins.