Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.

Cosmomycin D (CosD) is the major constituent fraction isolated from a culture of Streptomyces olindensis ICB20. The ability of this compound to intercalate with doublestranded DNA was studied by gel mobility shift assays and electrospray ionization mass spectrometry (ESI-MS). ESI-MS experiments showed that the complex of CosD with 16-mer double-stranded DNA was at least as stable as a complex of daunorubicin with the same DNA sequence. This is the first study showing DNA binding properties of an anthracycline Anthracyclines are an important family of natural products produced by microorganisms of the actinomycetes group. They are tetracyclic aromatic polyketides which share a 7,8,9,10-tetrahydrotetracene-5,12-quinone structure. Some members of the anthracycline group of antibiotics show interesting pharmaceutical, mostly anticancer, activities1,2). Anthracyclines that are used for cancer treatment include daunorubicin (Fig. 1A; DAU; daunomycin) and its hydroxylated derivative doxorubicin (Fig.

Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds.

Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to differences in structure between cosmomycin D and doxorubicin.

Herein, we report a draft genome sequence of the endophytic Curtobacterium sp. strain ER1/6, isolated from a surface-sterilized Citrus sinensis branch, and it presented the capability to control phytopathogens. Functional annotation of the ~3.4-Mb genome revealed 3,100 protein-coding genes, with many products related to known ecological and biotechnological aspects of this bacterium.

The effect of pH on cell growth and retamycin production in batch bioreactor cultures of Streptomyces olindensis ICB20 was investigated. In fermentations pH-controlled over the range 6.0-8.0, the highest retamycin production was achieved at pH 7.0, and the maximum concentration of retamycin, about 1.36 A (absorbance) units, was about 43, 58 and 232% higher than the values obtained at pH 7.5, 6.0 and 8.0 respectively.

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27Burkholderia species have different lifestyles establishing mutualist or pathogenic associations 28 with plants and animals. Changes in the ecological behavior of these bacteria may depend on 29 genetic variations in response to niche adaptation. Here, we studied 15 Burkholderia strains 30 isolated from different environments with respect to genetic and phenotypic traits. By 31Multilocus Sequence Analysis (MLSA) these isolates fell into 6 distinct groups. MLSA clusters 32 did not correlate with strain antibiotic sensitivity, but with the bacterial ability to produce 33 antimicrobial compounds and control orchid necrosis. Further, the B. seminalis strain 34 TC3.4.2R3, a mutualistic bacterium, was inoculated into orchid plants and the interaction with 35 the host was evaluated by analyzing the plant response and the bacterial oxidative stress 36 response in planta. TC3.4.2R3 responded to plant colonization by increasing its own growth 37 rate and by differential gene regulation upon oxidative stress caused by the plant, while 38 reducing the plant's membrane lipid peroxidation. The bacterial responses to oxidative stress 39 were recapitulated by bacterial exposure to the herbicide paraquat. We suggest that the ability 40of Burkholderia species to successfully establish in the rhizosphere correlates with genetic 41 variation, whereas traits associated with antibiotic resistance are more likely to be categorized 42 as strain specific. 43 44