1-Hydroxy-1-norresistomycin and Resistoflavin Methyl Ether: New Antibiotics from Marine-derived Streptomycetes†, ††

Abstract

Cultivation of the marine-derived streptomycete isolate B8005 delivered three known antibiotics, resistomycin (1), resistoflavin (3a) and tetracenomycin (4), and a further member of the rare resistomycin class, the weakly antibiotically active 1-hydroxy-1-norresistomycin (2). From a related marine strain B4842, 1 and resistoflavin methyl ether (3b) have been isolated. The formation of 2 is of interest from a biosynthetic point of view.Keywords resistomycin, 1-hydroxy-1-norresistomycin, marine streptomycetes, natural product, structure elucidationIn the course of our screening of streptomycetes for new bio-active secondary metabolites, extracts of the marine Streptomyces isolate B8005 showed inhibitory activity against Escherichia coli, Staphylococcus aureus, Streptomyces viridochromogenes (Tü 57), Mucor miehei, Candida albicans, and the microalga Chlorella vulgaris. Additionally it possessed cytotoxic activity against Artemia salina. In the TLC screening, the extract showed moderately polar yellow and red spots. Work-up delivered three known antibiotics, resistomycin (1) [1,2], resistoflavin (3a) [1,3] and tetracenomycin (4) [4], and a new resistomycin derivative, 1-hydroxy-1-norresistomycin (2), as a further active principle. From a second marine Streptomyces isolate B4842, resistoflavin methyl ether (3b) has been isolated, along with 1. Resistomycin (1) is a quinone-related antibiotic with unique structure and possesses bactericidal and vasoconstrictive activity. It inhibits RNA and protein synthesis, but has no effect on DNA synthesis [5]. It was so far the only further member of this type of compounds.The Streptomyces strain B8005 has been derived from sediment of the Laguna de Terminos at the Gulf of Mexico and was isolated on M3-medium [6]. The partial 16S rRNA gene sequence of the strain B8005 is identical with that of the strain Streptomyces albogriseolus (DSM 40003) and Streptomyces viridodiastaticus (DSM 40249). However, the strain B8005 differs from both strains in forming a chocolate brown substrate mycelium. The spore mass is gray, spore chains are spiral; the surface of spores is spiny. Melanin pigment is neither produced on peptone -yeastextract iron agar [7] nor on tyrosine agar [7] but a chocolate brown pigment is found in media like yeast -extract maltextract agar [8] and chitin agar [8]. The optimum growth temperature is at about 30°C. The strain does not grow at 10°C but shows growth at 45°C. Growth occurred in media from 0% up to 10% seawater salinity. Chitin, cellulose, starch, casein, gelatine, and esculin are degraded. The strain is catalase and nitrate reductase positive. The use of

Marine Streptomyces as a novel source of bioactive substances

“…This is an inhibitor of HIV-1 protease. Resistoflavine (13) is produced by S. chibaensis AUBN (1)/7 (Kock et al 2005;Gorajana et al 2006). The structures of the quinones discussed above are displayed in Fig.…”

Antitumor Compounds from Marine Actinomycetes

“…These compounds together with resistomycin and tetracenomycin D are produced by Streptomyces sp. B8005 isolated from sediments of the Laguna de Términos at the Gulf of México [88]. Resistomycin was isolated, in addition, from Streptomyces sp.…”

Marinamide, a novel alkaloid and its methyl ester produced by the application of mixed fermentation technique to two mangrove endophytic fungi from the South China Sea

“…Marine microorganisms have developed unique metabolic pathways because of the special marine environment and its special functions in the ecosystem, and provided a lot of metabolites not produced by terrestrial microorganisms. Recently, a lot of bioactive metabolites with novel structure were isolated continuously from marine fungi [2][3][4][5] , marine actinomycetes [6][7][8][9][10] and marine bacteria [11][12][13][14] . From the 1990s, we began to screen for novel bioactive metabolites from marine-derived mangrove endophytic fungi from the South China Sea, and found many significant novel structures [15][16][17][18][19][20][21][22][23][24][25] .…”