Streptomyces sp. BV410. a) Growth and appearance on MSF agar (mannitol 2%, soybean flour 2%, agar 2%) at 30°C for 4 days. b) Scanning electron micrographs of BV410 grown on MSF agar for 7 days at 30°C showing mycelia and spore chains. c) Phylogenetic tree of 12 strains of Streptomyces spp. based on the 16S rDNA gene sequence. Sequences of 11 type strains and an outgroup sequence (Bacillus subtilis MF993342.1) were obtained from the GenBank. BV410 is marked with a square. The numbers at the branching points are the percentages of occurrence in 1,000 bootstrapped trees. The bar indicates a distance of 0.020 substitutions per site

HPLC analysis and fractionation of the BV410 crude extract. The crude extract was collected as multiple fractions (red bars) which were individually tested for antifungal activity. Fraction 6 (*) with a retention time of 14.5–15.5 min showed potent antifungal activity. Fraction 6 was further purified, and a UV absorbance spectrum was obtained (inlet)

Optimization of staurosporine production in Streptomyces sp. BV410 (a) Biomass (wet weight; in grams per liter) and (b) staurosporine (in milligrams per gram of wet mycelia) concentration in cultures grown for 7 () and 14 () days at 28°C and 200 rpm in five different media (JS, JSYE, JSYEP, TSB, and R2YE). (c) Staurosporine yield (in milligrams per liter of culture) from cultures grown in JS medium for 14 days, with the initial pH values adjusted to 6.5, 7.5, and 8.5 and with the addition of supplements (methyl oleate, ZnSO_4, and FeSO₄)

Toxicity assessment of staurosporine in the zebrafish model. (a) The dose‐dependent survival/teratogenicity, (b, c) cardio‐ and hepatotoxicity, and (d, e) myelotoxicity are shown. At a staurosporine dose of 50 ng/ml, embryos were seriously affected, showing large pericardial edema (solid arrow), reduced and damaged liver (white arrow) and whole‐body edema (b). The changes in the liver area index assessed in 120‐hr old zebrafish embryos were not observed between DMSO‐treated (Control) and staurosporine‐treated embryos (35 ng/ml), contrary to the group upon a dose of 50 ng/ml (c). Staurosporine was not myelotoxic at doses up to 35 ng/ml, while at 35 ng/ml, it caused weak neutropenia in the treated zebrafish embryos, as detected at 72 hpf. *p < .05, **p < .01, ***p < .0001

Antiangiogenic activity of staurosporine evaluated in the transgenic Tg(fli1:EGFP) zebrafish model. A dose‐dependent reduction of a) the number of intact ISV vessels, b) ISV length, and c) SIV basket length. d) Morphology and antiangiogenic phenotype of embryos treated with the antiangiogenic drug sunitinib malate (1.25 µmol/L = 665.7 ng/ml) and 1 ng/ml and 20 ng/ml of staurosporine (2.1 nmol/L and 42.9 nmol/L, respectively)