|Title||Streptomyces artemisiae MCCB 248 isolated from Arctic fjord sediments has unique PKS and NRPS biosynthetic genes and produces potential new anticancer natural products|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Dhaneesha M., Naman C.B, Krishnan K.P, Sinha R.K, Jayesh P., Joseph V., Singh I.SB, Gerwick WH, Sajeevan T.P|
|Type of Article||Article|
|Keywords||a-d; actinomycete; actinomycetes; antibiotics; anticancer; apoptosis; biological-activity; diversity; genus marinispora; marine; metabolites; natural products; polyene-polyol macrolides; polyketide synthase genes; Streptomyces|
After screening marine actinomycetes isolated from sediment samples collected from the Arctic fjord Kongsfjorden for potential anticancer activity, an isolate identified as Streptomyces artemisiae MCCB 248 exhibited promising results against the NCI-H460 human lung cancer cell line. H460 cells treated with the ethyl acetate extract of strain MCCB 248 and stained with Hoechst 33342 showed clear signs of apoptosis, including shrinkage of the cell nucleus, DNA fragmentation and chromatin condensation. Further to this treated cells showed indications of early apoptotic cell death, including a significant proportion of Annexin V positive staining and evidence of DNA damage as observed in the TUNEL assay. Amplified PKS 1 and NRPS genes involved in secondary metabolite production showed only 82% similarity to known biosynthetic genes of Streptomyces, indicating the likely production of a novel secondary metabolite in this extract. Additionally, chemical dereplication efforts using LC-MS/MS molecular networking suggested the presence of a series of undescribed tetraene polyols. Taken together, these results revealed that this Arctic S. artemisiae strain MCCB 248 is a promising candidate for natural products drug discovery and genome mining for potential anticancer agents.