Amycolatopsis mediterranei Rifamycins

Zhang, W.W. Jiang, W.H. Zhao, G.P. Yang, Y.L. Chiao, J.S. Expression in Escherichia coli, purification and kinetic analysis of the aspartokinase and aspartate semialdehyde dehydrogenase from the rifamycin SV-producing Amycolatopsis mediterranei U32. Appl. Microbiol. Biotechnol., 54, 52-58 (2000)... 

The rifamycins are ansamycin antibiotics produced by cultures of Amycolatopsis mediterranei (formerly Nocardia mediterranei or Streptomyces mediterranei). The crude antibiotic mixture was found to contain five closely related substances rifamycins A-E, but if the organism was cultured in the presence of sodium diethyl barbiturate (barbitone or barbital), the product was almost entirely rifamycin B (Figure 3.71). Rifamycin B has essentially no antibacterial activity, but on standing in aqueous solution in the presence of air, it is readily transformed by oxidation and intramolecular nucleophilic addition into rifamycin O, which... 

Ning, S., Muller, R.,Yu,T.W.,Taylor, M., Hoffmann, D., Kim, C. G., Zhang, X., Hutchinson, C. R., Floss, H. G., Biosynthesis of the ansamycin antibiotic rifamycin deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699, Chem Biol. 1998, 5, 69-79. 

Rifamycin B, produced by Amycolatopsis mediterranei, is one of the most notable members of the ansamycin family [36, 37, 64, 65] (Fig. 14). It has been used clinically in a synthetically modified form called rifampicin and it is still one of the first-line therapies effective in the treatment of tuberculosis and other mycobacterial infections. The starter unit for rifamycin polyketide assembly is part of the chromophore and is derived from 3-amino-5-hydroxybenzoic acid. Five polyketide synthases are involved in the formation of rifamycin chromophore and the first polyketide synthase contains at the N terminus the loading domain for 3-amino-5-hydroxybenzoic acid, which consists of an acyl-CoA ligase linked to ACP, and module 1-3. The rifamycin polyketide synthase lacks a TE domain at the C terminus. The release of polyketide chain from polyketide synthase and the formation of amide to generate the macrocyclic lactam will be catalyzed by RifF, which is very similar to arylamine A-acetyltransferase. 

Schupp, T., Toupet, C., Engel, N., and Goff, S. (1998). Cloning and sequence analysis of the putative rifamycin polyketide synthase gene cluster from Amycolatopsis mediterranei. FEMS Microbiol. Lett. 159, 201-207. 

Rifamycins belong to a group of antibiotics some of which are biosynthesized in fermentation cultures by the bacterium Amycolatopsis rifamyci-nica while some are sanisynthelic compounds prepared by derivitization. The name of the bacterium that produces rifamycins has evolved from the original Streptomyces mediterranei to Nocardia mediterranei, then to Amycolatopsis mediterranei, and in 2004 to A. rifamycinica. 

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