Sorangium cellulosum, epothilones from

More recently two functionally redundant Sfp-type PPTase, MxPptl and MxPptZ, have been found to differentially activate biosynthetic pathways in Myxococcus xanthus MxPptl and MxPptZ exhibit broad substrate specificity as supported by the fact that the complex PKS-NRPS hydrids epothilone and myxothiazol from Sorangium cellulosum and Stigmatella aurantiaca, respectively, could be expressed in M. xanthus without the need for an external PPTase. 

Epothilones A-E (3, 17, 48-50, Fig. 12) were isolated by Hofle and Reichen-bach and co-workers from the myxobacterium Sorangium cellulosum [80, 81]. After initial selection for their antifungal activity, the epothilones were soon shown to possess significant cytotoxicity against mammalian cells, epothilone B being the most active one [82]. Their mode of action was shown to be microtubule stabilization in a fashion very similar to that of... 

After the identification of the paclitaxel mechanism of action, several additional microtubule stabilizing agents were discovered from natural sources (Chart 9). Among them, epothilones (12-15) are the most studied and characterized. Epothilones A and B (12,13) were first isolated by Hofle and coworkers [54] from a myxobacterium (Sorangium cellulosum strain 90) in 1993, while their activity in stabilizing microtubule similarly to paclitaxel was reported for the first time by Bollag and co-workers in 1995 [55], Experiments with radio-labeled paclitaxel... 

Patupilone (epothilone B, EPO906) 29 (Novartis) is being evaluated in a Phase III trial for the treatment of patients with ovarian, primary fallopian or peritoneal cancer.191,196,197 Patupilone (then called epothilone B) 29 was first reported by Hofle and co-workers198 200 31 from the myxobacterium Sorangium cellulosum in a 1991 patent application and epothilones were shown by workers at Merck in 1995 to have tubulin-stabilising activity similar to that of paclitaxel 60.31 Ixabepilone 28, which is the semi-synthetic lactam derivative of patupilone 29, was the first epothilone derivative approved (October 2007) for the treatment of breast cancer. 

Gerth K, Bedorf N, Hofle G, Irschik H, Reichenbach H. 97. Epothilons A and B antifungal and cytotoxic compounds from Sorangium cellulosum Myxobacteria. Production, physicochemical and biological properties. J. Antibiot. (Tokyo) 1996 49 560-563. 98. 

Epothilones A (56) and B (57), 16-membered macrocyclic polyketide lactones, were first isolated from the cellulose-degrading myxobac-terium Sorangium cellulosum by Hoefle, Reichenbach, and coworkers (86) as narrow-... 

A recent example of the power of this technique when applied to natural products is the development of an efficient method for scale-up produchon of epothilone D (Figure 8.6), which entered clinical trials as a potential anticancer agent but has now been disconhnued in favor of a congener, 9,10-didehydroepothilone D. Epothilone D was the most active of the epothilone series isolated from the myxobacte-rium, Sorangium cellulosum, and is the des-epoxy precursor... 

Julien, B., Shah, S., Ziemann, R., Goldman, R., Katz, L., Khosla, C. Isolation and characterization of the epothilone biosynthetic gene cluster from Sorangium cellulosum. Gene 2000, 249, 153-160. 

An example of particular interest is epothilone from Sorangium cellulosum So ce90, which has recentiy been approved for the treatment of breast cancer. Epothilone inhibits microtubule depolymerization and is active against multidrug-resistant cancer cell lines and paclitaxel-resistant tumors. The most comprehensively characterized and so far only epothilone derivative, which received FDA approval for clinical use, is ixabepi-lone. The compound is marketed in the US by Bristol-Myers Squibb (BMS) under the trade name Ixembra . 

Epothilones, isolated from the mycobacterium Sorangium cellulosum in 1996, are a new class of cytotoxic macrolides that are especially effective against drug-resistant tumor cell lines by the same mechanism as the taxoids. The structural feature of epothilones (Fig. 1) includes a 16-membered lactone ring, p-hydroxyl carbonyl units and cw-epoxide on the macrocyclic ring, and a thiazole unit as the side chain. 

Heterologous Expression of the Epothilone Gene Cluster from Sorangium cellulosum in Myxococcus xanthus 471... 

The Anticancer Drug Ixabepilone is a Derivative of Epothilone from Sorangium cellulosum So ce90 474... 

Molnar, I., Schupp, T., Ono, M., Zirkle, R. et al (2000) The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. Chem. Biol, 7 (2), 97-109. 

Epothilones are a class of novel compounds first isolated from the bacterium Sorangium cellulosum in Southern Africa. 

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