A set of 600 actinomycetes strains which were isolated from marine sediments from various sites in the Pacific and Atlantic Oceans were screened for the production of bioactive secondary metabolites. Marine streptomycete strains were found to be producers of well known chemically diverse antibiotics isolated from terrestrial streptomycetes, as in the case of marine Micromonospora strains. New marine members of the rare genus Verrucosispora seem to be a promising source for novel bioactive secondary metabolites as shown in the case of the abyssomicin producing strain AB-18-032.

Caboxamycin, a new benzoxazole antibiotic, was detected by HPLC-diode array screening in extracts of the marine strain Streptomyces sp. NTK 937, which was isolated from deep-sea sediment collected in the Canary Basin. The structure of caboxamycin was determined by mass spectrometry, NMR experiments and X-ray analysis. It showed inhibitory activity against Gram-positive bacteria, selected human tumor cell lines and the enzyme phosphodiesterase.

A family of three novel aminofuran antibiotics named as proximicins was isolated from the marine Verrucosispora strain MG-37. Proximicin A was detected in parallel in the marine abyssomicin producer "Verrucosispora maris" AB-18-032. The characteristic structural element of proximicins is 4-amino-furan-2-carboxylic acid, a hitherto unknown g -amino acid. Proximicins show a weak antibacterial activity but a strong cytostatic effect to various human tumor cell lines.

Six genes (nikP1, nikP2, nikS, nikT, nikU, and nikV) from Streptomyces tendae Tu901 were identified by analysis of the nucleotide sequence of the nikkomycin gene cluster. These genes, together with the previously described nikQ and nikR, span 9.39 kb and are transcribed as a polycistronic mRNA in a growth-phase-dependent manner. The nikP1 gene encodes a non-ribosomal peptide synthase consisting of an adenylation domain, a thiolation domain, and an N-terminal 70-residue segment of unknown function. The amino acid sequence encoded by the nikP2 gene displays similarity to the sequences of thioesterases, and the nikS product belongs to a superfamily of proteins characterized by a specific ATP-binding fold. The N-terminal 70 amino acids of the predicted nikT gene product show significant sequence similarity to acyl carrier proteins, and the C-terminal 330 amino acids to aminotransferases. The sequences of the deduced proteins NikU and NikV exhibit similarity to components S and E, respectively, of glutamate mutase from Clostridium. Disruption of the nikP1, nikS, nikT, or nikV gene by insertion of a kanamycin resistance cassette abolished formation of nikkomycins I, J, X, and Z, all of which contain hydroxypyridylhomothreonine as the peptidyl moiety. The nikP1 mutants, and the nikS and nikT mutants accumulated the nucleoside moieties nikkomycin Cz, and nikkomycins Cx and Cz, respectively. The nikV mutants formed nikkomycins Ox and Oz, which contain 2-amino-4-hydroxy-4-(3'-hydroxy-6'-pyridyl) butanoic acid as the peptidyl moiety. The nikP2 mutants synthesized nikkomycins I, J, X, and Z, but amounts of nikkomycins I and X, which contain formylimidazolone as the base, were lower. Feeding formylimidazolone to nikP2 mutants restored the ability to form nikkomycins I and X. Our results indicate that nikU and nikV are required for the synthesis of hydroxypyridylhomothreonine, the genes nikP1, nikP2 and nikS are required for the assembly of nikkomycins, and nikT is required for both pathways. The putative activities of each of their products are discussed.

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Drugs from the sea: Three new netropsin‐type antibiotics (1–3) with a hitherto unknown furan core structure have been isolated from marine actinomycete strains and their structures elucidated by means of mass spectrometry and 2D NMR spectroscopy. The compounds show antitumor activity and, in contrast to netropsin, they induce upregulation of p53 and the cyclin kinase inhibitor p21.

Protein P8 was previously identified as a putative nikkomycin biosynthesis protein. The gene (nikC) encoding protein P8 was cloned from the Streptomyces tendae Tü901 nikkomycin gene cluster and sequenced. The nikC gene was inactivated by inserting a kanamycin resistance cassette; the mutant did not produce the biologically active nikkomycins I, J, X, and Z, but accumulated the nucleoside moieties nikkomycins C X and C Z . The mutant was complemented to nikkomycin production (I, J, X, Z) by nikC expressed from the mel promoter of the vector pIJ702. Furthermore, the nikkomycin-negative phenotype was reversed by the addition of picolinic acid, a precursor of the peptidyl moiety of nikkomycins (nikkomycin D), into the culture medium. The nikC gene was expressed in Escherichia coli and identified and characterized at the enzyme level. NikC encodes an L-lysine 2-aminotransferase, and the activity was exclusively detected in nikkomycin producers and its presence correlated to nikkomycin production. The nikC-inactivated mutant grew with L-lysine as sole source of nitrogen and carbon, indicating that L-lysine 2-aminotransferase is not required for lysine catabolism. Our results identified the nikC-encoded L-lysine 2-aminotransferase as the nikkomycin biosynthetic enzyme that catalyzes the initial reaction in nikkomycin D biosynthesis. The NikC protein belongs to a novel family of pyridoxamine or pyridoxal-phosphate-dependent dehydrases and aminotransferases, some of which are involved in dideoxy-and deoxyaminosugar biosynthesis.Keywords : nikkomycin ; Streptomyces; lysine aminotransferase ; antibiotic production; secondary metabolism.Nikkomycins X and Z exhibit high antifungal, insecticidal, Nikkomycins are peptidyl nucleoside antibiotics that act as and acaricidal activity [7]. Since nikkomycins are nearly nonspecific and competitive inhibitors of chitin synthases from toxic for bees and mammals and are easily degraded in nature, fungi and insects [1Ϫ3]. Streptomyces tendae Tü901 produces they have the potential to be applied as insecticides in agriculvarious types of nikkomycin, and the main components of the ture or as antifungal agents in human therapy [8, 9]. Growth culture filtrate are nikkomycins I, J, X, and Z (Fig. 1). The peptiof Candida albicans is only inhibited at high concentrations of dyl moiety of these nikkomycins is hydroxypyridylhomothreonikkomycin X and Z [10], but combinations of nikkomycin with nine (nikkomycin D), and the nucleoside moiety consists of an antimycotically active azoles, which are directed against the funaminohexuronic acid with N-glycosidically bound 4-formyl-4-gal cytoplasmic membrane, are efficacious in treating mycosis in imidazoline-2-one (nikkomycin C X ) or uracil (nikkomycin C Z ) animals [11]. Nikkomycin Z is very effective against the highly [4]. Both moieties constitute A-amino acid structures that are chitinous, dimorphic fungal pathogens Coccidioides immitis, connected via a peptide bond to yield the dipeptidyl nikkomyBlastomyces dermatitidis, and Histoplasma capsulatum [...

A new angucyclinone antibiotic, frigocyclinone, was isolated from Streptomyces griseus strain NTK 97, consisting of a tetrangomycin moiety attached through a C-glycosidic linkage with the aminodeoxysugar ossamine. Frigocyclinone showed antibacterial activities against Gram-positive bacteria. Keywords angucyclinone, screening, antibacterial, antibiotic, Streptomyces griseusIn our HPLC-diode array screening program to detect novel secondary metabolites from actinomycetes isolated from extreme habitats, extracts of culture filtrates of strain NTK 97 drew our attention. Strain NTK 97 was isolated from a terrestrial sample from Terra Nova Bay at Edmundson Point, Antarctica and produced a prominent metabolite whose UV-visible spectrum and retention time were compared with those of the more than 770 reference compounds stored in our HPLC-UV-Vis-Database [2]. The UV-visible spectrum of the dominant compound was highly similar to that of urdamycin B produced by Streptomyces fradiae [3], but their retention times differed significantly. The structure of the isolated metabolite was elucidated as a new angucyclinone with a C-glycosidic linked ossamine sugar moiety and was named frigocyclinone (1). The structure is shown in Fig. 1.Strain NTK 97 was examined for a number of key properties known to be of value in streptomycete systematics [4]. The presence of LL-diaminopimelic acid in the peptidoglycan [5] together with its colonial characteristics [6] allowed its assignment to the genus Streptomyces. More detailed taxonomic studies showed that the organism was a bone fide Streptomyces griseus strain as it produced a grey aerial spore mass on oatmeal agar, formed straigth to flexuous chains of smooth-surfaced spores and shared very high 16S rRNA gene sequences (99.6ϳ99.7%) with members of this taxon [7].Batch fermentations of Streptomyces griseus strain NTK 97 were carried out in 10-liter stirred tank fermenters (New Brunswick). The production medium consisted of glucose 1%, starch 2%, Bacto peptone 0.3%, meat extract (Oxoid) 0.3%, yeast extract (Ohly Kat G, Deutsche Hefewerke) 0.5%, and CaCO 3 0.3% in tap water (pH 7.0). The fermentation was conducted at 27°C for 118 hours with an aeration rate of 0.5 v/v/m and an agitation of 200 rpm. The