Sorangium

The capacity of the genus Sorangium has raised considerable attention and motivated the corresponding myxobacterial genome project of the representative 

cellulosum So ce56, the genome sequence enabled the identification of the biosynthetic gene clusters for the etnangien antibacterials and the highly cytotoxic actin binders chivosazols [148,149]. 

The Anticancer Drug Ixabepilone Is a Derivative of Epothilone from Sorangium cellulosum So ce90 

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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. 

Ixabepilone (38 Ixempra, BMS-247550 Bristol-Myers Squibb, 2007), a semi-synthetic derivative of epothilone B (39) produced by Sorangium cellulosum, was developed by Bristol-Myers Squibb (BMS) as an anticancer drug (administered through injection) that binds directly to (3-tubulin subunits on microtubules, leading to suppression of microtubule dynamics, blocking of cells in the mitotic phase and ultimately leading to... 

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... 

Molnar 1, Schupp T, Ono M, et al. (2000) The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium ceUulosum So ce90. Chem. Biol. 7 97-109. 

Sorangium cellulosum is an ubiquitous soil bacterium that belongs to the order Myxococcales. It has the ability to glide over solid surfaces, to live in a biofilm and form fruiting bodies. Members of this taxon are a particularly rich source of metabolites with remarkable biological activities [177]. From one strain, another example of N-acyl-4-methoxy-3-pyrrolin-2-ones has been isolated. Eliamid (110) has been claimed to have cytostatic, nematocidal and fungicidal activities [178]. 

From strains of Sorangium cellulosum a chlorodivinylether, maracen (110), was isolated. It is active against Mycobacterium tuberculosis (IC99 < 12.5 pg/ml) and only slightly toxic against murine fibroblasts L929 (> 24 pg/ml) [89]. 

Herrmann M, Bohlendorf B, Irschik H, Reichenbach H, Hofle G (1998) Maracin and Maracen New Types of Ethynyl Vinyl Ether and a-Chloro Divinyl Ether Antibiotics from Sorangium cellulosum with Specific Activity Against Mycobacteria. Angew Chem Int Ed 37 1253... 

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... 

Gerth, K., Pradella, S., Perlova, O., Beyer, S., and Muller, R. 2003. Myxobacteria proficient producer of novel natural products with various biological activities-past and future biotechnological aspects with the focus on the genus Sorangium. J. Bio-technol., 106(2-3), 233-253. 

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. 

The major products originally isolated from the myxobacterium Sorangium cel-lulosum Sc 90 are epothilone A and epothilone B (Epo A and B), but numerous related members of this natural products family have subsequently been isolated as minor components from fermentations of myxobacteria. The relative and absolute stereochemistry of Epo B was determined by Hofle et al. in 1996 based on a combination of x-ray crystallography and chemical degradation studies, and the... 

Schneiker S, et al. Complete genome sequence of the myxobac-terium Sorangium ceUulosum. Nat. Biotechnol. 2007 25 1281-1289. 

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-... 

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