Actinomadura

Madurastatins A1 (119 Scheme 11.17), A2 (120), A3 (121), B1 (122), and B2 (123) were isolated in 2004 from a clinical isolate of a pathogenic actinomycete, a strain of Actinomadura madurae [189]. The stereochemistry of the N-methyl-N-hydrox-yornithine residue remains unknown, but it was determined that the serine and aziridine residues are D, and the rest are L. 

Trujillo, M. E. Goodfellow, M. Polyphasic taxonomic study of clinically significant actinomadurae including the description of Actinomadura latina sp. nov. Zbl. Bakt. 1997, 285, 212-233. 

Van Lanen, S.G., Oh, T.J., Liu, W. et al. (2007) Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis. Journal of the American Chemical Society, 129, 13082. 

Desferrimaduraferrin is a Fe " complexing metabolite of Actinomadura madurae 185). It consists of salicylic acid, p-Ala, Gly, L-Ser and 77 -hydroxy-77 -methyl-L-Om, with the latter incorporated in a heterocyclic system (Fig. 4, 13). From the same species the madurastatin group was obtained 136). The main representative A1 shows the sequence salicylic acid, o-azaridine carboxylic acid, L-Ala, p-Ala, 77 -hydroxy-77 -methyl-Om, L-cOHOm (Fig. 4, 14). In A2 the azaridine ring is opened giving a Ser residue, A3 is an isomer of the open form with the salicylic acid bound to the hydroxy group of Ser. B1 and B2 are the precursors A-salicyloyl-azaridine carboxylic acid and A-salicyloyl-Ser. The madurastatin species A1 forms a 1 1 Fe " complex as shown by mass spectrometry. 

Hantke K, Nicholson G. Rabsch W, Winkelmann G (2003) Salmochelins, Siderophores of Salmonella enterica and Uropathogenic Escherichia coli Strains, are Recognized by the Outer Membrane Receptor Iron. Proc Natl Acad Sci USA 100 3677 Harada K, Tomita K, Fuji K, Masuda K, Mikami Y, Yazawa K, Komaki H (2004) Isolation and Structural Characterization of Siderophores, Madurastatins, Produced by a Pathogenic Actinomadura madurae. J Antibiot 57 125... 

S. staurosporeus Anaya Actinomadura madurae A. melliaura Arcyria denudata Aspergillus flavus A. tubingensis Nocardia aerocoligenes Nocardiopsis dassonvillei Nocardiopsis sp. 

In 1997, Seto et al. reported the isolation of the novel neuronal protecting substances, carbazomadurin A (256) and carbazomaduiin B (257) from Actinomadura madurae 2808-SVl. Carbazomadurin B (257) was isolated from Nature in optically active form [a]p -I- 4.0 (c 0.05, MeOH). However, the absolute configuration was not determined (229) (Scheme 2.63). 

In 2005, Han et al. reported the isolation of a novel, naturally occurring, staurosporine analog, ZHD-0501 (321) from the fermentation broth of a marine-derived Actinomadura sp. 007. This was the first example of a staurosporine analog carrying a heterocycle fused to the pyran ring, and it has shown in vitro anticancer activity against mammalian cancer cells. In nature, this isolate was obtained in its optically active form [a]p -I- 83.2 (c 0.10, MeOH) (306). 

Oxanthromicin (79) (Figure 33) is an optically active antibiotic that has been isolated from the fermentation broth produced by Actinomadura sp. SCC 1646 ° . The results... 

Pept verucopeptin Actinomadura verrucosospora, Bact. from the Philippines Sugawara 1993) vancomycin (Streptomyces orientalis, Actinom., Bact. from Borneo soil MI) caerulein-like (from Australian tree frog, Litoria splendida, and Hyla caerulea, Amphib. from W Australia Wabnitz 1999). 

The antimicrobial pyralomycins have been isolated from a culture of Actinomadura spiralis strain. Pyralomycins la-Id (95-98) have a cyclohexene ring connected to the benzopyranopyrrole chromophor. 

Neostdomycin (Ci7H2oN2C>6) and SF-2140 (L 7.11- NO. are indole N-glycosidcs produced by S. try gro.t copious and Actinomadura, respectively. Both show activity against gram-positive bacteria, yeast, fungi, and viruses. 

Decatromicins A (1218) and B (1219) are produced by an Actinomadura sp. and are active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (1229,1230). These compounds are closely related to pyrrolosporin A (1220) from Micromonospora sp. (1231,1232). The ascidian Polycitor africanus from Madagascar has afforded the new polycitone B (1221) (1233), which is related to the known polycitone A (1), a potent inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (1234). The known polycitrin B was synthesized for the first time (1235). 

The previously known kedarcidin chromophore (7) is revised to CCC (7559), and the mechanism of action of this enediyne has been studied (1560). The new maduropeptin chromophore 1601 was isolated from Actinomadura madurae, which is associated with a protein of 14 amino acids (1561-1563). The non-protein associated enediyne N1999A2 (1602) was characterized from Streptomyces sp. AJ 9493 (1564), and confirmed by synthesis (1565,1566). 

Momose I, IinumaH, KinoshitaN, Momose Y, KunimotoS, HamadaM, Takeuchi T (1999) Decatromicins A and B, New Antibiotics Produced by Actinomadura sp. MK73-NF4 I. Taxonomy, Isolation, Physico-Chemical Properties and Biological Activities. J Antibiot 52 781... 

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