Actinomycetal metabolites

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. 

Asterobactin from Nocardia asteroides 257) contains salicylic, 2,3-dihydroxy-propionic, and 2-methyl-3-hydroxyundecanoic acid as well as derivatized Om and Arg residues (Fig. 4, 15). It forms a Fe complex. The stereochemistry of the various centers was not determined but L-configuration is proposed for Om and Arg for biosynthetic reasons (general amino acid pool) and a negative of asterobactin. Whether the three compounds are involved in metal transport has not been investigated. 

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Oxidation of the protected 5-aminoindole 129 with Dess-Martin periodinane (DMP) produced the indole-quinone 130. This methodology was employed in a new total synthesis of the Actinomycetes metabolite BE-10988 (131), which is a promising topoisomerase II inhibitor <02JA2221>. 

Magarvey NA, JM Keller, V Bernan, M Dworkin, DH Sherman (2004) Isolation and characterization of novel marine-derived actinomycete taxa rich in bioactive metabolites. Appl Environ Microbiol 70 7529-7530. 

Li, W., Josephs, J.L., Skiles, G. and Humphreys, W.G. (2008) Metabolite generation via microbial biotransformation with actinomycetes rapid screening methods and synthesis of important human metabolites of two development stage compounds, BMS-587101 and dasatinib. Drug Metabolism and Disposition The Biological Fate of Chemicals, 36, 721-730. 

Tephrosone 33, a flavonoid belonging to the tephrorin family (vide supra), was found to possess a dihydrobenzofuran framework . Moreover, a metabolite of Penicillium brevicompactum, namely brevione A 34 was found to contain a spiro system . Neomarinone 35, another metabolite from a marine actinomycete, constitutes an intriguing sesquiterpenoid skeleton <00TL2073>. 

Actinomycetes can metabolize a wide variety of organic substrates, including organic compounds that are generally not metabolized, such as phenols and steroids. They are also important in the metabolism of heterocyclic compounds such as complex nitrogen compounds and pyrimidines [42,49]. The breakdown products of their metabolites are frequently aromatic, and these metabolites are important in the formation of humic substances and soil humus [42,49]. 

GERBER, N.N., Three Highly Odorous Metabolites from an Actinomycete. 2-Isopropyl-3-methoxypyrazine, Methylisobomeol, and Geosmin , J Chem Ecol 3 475 (1977). 

Stmcturally closely related is the Nocardia metabolite, siderochelin, for which the structure and relative and absolute stereochemistry were aU established by X-ray crystallography (208, 267). It is a mixture of two epimers A and B (Fig. 29, 82 and 83). Siderochelin C, with an ethyl residue (Fig. 29,84), was obtained from a different actinomycete, tentatively identified as Streptoalloteichus sp. (239). 

The Panamanian marine area has afforded unique microbial metabolites. Unusual polyene polyketides, the macrolactins, were isolated from a deep-sea bacterium in culture. Unfortunately the strain has been lost, or has lost viability (Rychnovsky1992). Unique cyclic heptapeptides, the cyclomarins, were obtained from the culture of an actinomycete, Streptomyces sp., isolated from sediments. The uniqueness of these metaboEtes contradicts the common assumption of scarce boundaries posed to microbial species m the sea. 

Sitachitta, N. Gadepalli, M Davidson, B.S. (1996) New a-pyrone-containing metabolites from a marine-derived actinomycete. Tetrahedron, 52, 8073-80. 

Vancoresmycin (125) is a metabolite extacted from the mycelium of an actinomycete strain of the genus Amycolatopsin sp. It exhibited potent activity against gram-positive bacteria, including vancomycin-resistant strains such as Enterococcus spp. [191], but was inactive towards gramnegative bacteria and showed no fungal activity. The plane structure was derived from MS and NMR studies which also revealed the stereochem-... 

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