8% at concentration of 10 μM, but had no cytotoxic activities against gastric cancer cells (BGC-823) and breast cancer cells (MCF7). Compound 6 showed a moderate activity against gastric cancer cells (BGC-823) with inhibition value of 48% at concentration of 1 μM and had weaker cytotoxic activity against lung cancer cells (A549). Kiamycin (compound 5) exhibited weaker inhibition
activity against gastric cancer cells (BGC-823) and had no cytotoxic activities against lung cancer cells (A549) and breast cancer cells (MCF7). The results indicated that the compounds 2 and 6 might have potential selective target against the cancer cells, as shown in Table 2. In this study, Gefitinib price the draft genome sequence of Streptomyces sp. W007 contained an intact biosynthetic gene cluster for angucyclinone antibiotics, which provided insight into the biosynthesis of angucyclinone antibiotics.
Meanwhile, two novel and four known angucyclinone antibiotics were isolated from the culture broth of marine NU7441 price Streptomyces sp. W007. We have already defined the chemical structure and cytotoxicities of these angucyclinone antibiotics, but the biosynthetic pathways remain unclear. We focus research on biosynthetic pathways of the two new compounds and elucidate 22-kb DNA fragment containing type II PKS genes involved in the biosynthesis of compound 1 and kiamycin. Two primary transporters (ABC transporter-related protein and EmrB/QacA family drug resistance transporter) Thiamine-diphosphate kinase and two regulators (LuxR family transcriptional regulator and TetR family transcriptional regulator) existed in the gene cluster of aromatic polyketide and might have important roles on the synthesis, regulation, and release of secondary metabolites. The detection of some genes with sequence similarity to the biosynthetic gene clusters of the angucycline antibiotics urdamycin A (Decker & Haag, 1995), jadomycin B (Han et al., 1994), simocyclinone (Galm et al., 2002), hatomarubigin (Kawasaki et al.,
2010), oviedomycin (Lombó et al., 2004), sch47554, and sch47555 (Basnet et al., 2006) strongly suggested that the identified DNA sequence indeed represented the compound 1 biosynthetic gene cluster. However, it is characteristic of compound 1 to contain methoxyl group at C-8 and no keto or hydroxy groups at C-7 and C-12, which was in accordance with analysis of the biosynthesis gene of angucyclinone antibiotic. There is O-methyltransferase gene (ang 10) in the cluster with high percent identity to related gene in Streptomyces sp. 2238-SVT4 (Kawasaki et al., 2010). This O-methyltransferase catalyzed the methoxylation reaction on the –OH of C-8. Ang 5, ang 7, and ang 18 are oxygenase reductases and should catalyze the 6, 7, 8-hydroxylation and dehydration reaction to generate compound 1. In this case, marine Streptomyces sp.
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