Epothilones are 16-membered ring macrolides originally isolated from Sorangium cellulosum Soce90 that kill dividing cells by stabilizing microtubules. Previously, S. cellulosum So0157-2 was found to produce epothilones, with production of epothilones A and B optimized to industrial scales and five new glycoside derivatives isolated. As part of ongoing efforts to discover new epothilones from this strain, we focused on minor and polar components from large-scale fermentations. The strain was cultivated in 70 l M26 medium, and through repeated column chromatography (Sephadex LH-20, RP-18, silica gel) and HPLC (C18 column, 65% methanol elution), two new epothilone-type 18-membered ring macrolides (named epothilones M and N) were isolated, along with known epothilones A9, A, B, and C. Their structures were established via HR quadrupole time-of-flight MS and NMR data: epothilone M (1) is an 18-membered macrolide with an ester bond between the oxymethylene group (H-17) and carboxyl group (C-1), while epothilone N (2) is 12,13-deepoxy-12-chloro-13-hydroxyl epothilone M. Cytotoxic activity against the MDA-MB-435 cell line (MTT method) showed epothilone M (IC50 0.12 μM) and epothilone A9 (IC50 0.26 μM) had similar activity, whereas epothilone N (IC50 2.47 μM) exhibited modest activity. These 18-membered epothilones from a wild-type strain represent a new structural type of epothilones, and their in vitro cytotoxicity suggests potential for antitumor drug discovery, with bioengineering of the strain to produce more derivatives and in vivo activity testing warranted.