Antitumor Actinopyranones Produced by Streptomyces albus POR-04-15-053 Isolated from a Marine Sediment

Abstract

Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and PM060431 (4), were isolated from the cell extract of the marine-derived Streptomyces albus POR-04-15-053. Their structures were elucidated by a combination of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS. They consist of an α-methoxy-γ-pyrone ring containing a highly substituted tetraene side chain glycosylated at C-10 in the case of 1 and 4. Compounds 1 and 4 displayed strong cytotoxicity against three human tumor cell lines with GI₅₀ values in the submicromolar range, whereas 2 showed subnanomolar activity as an inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of EGF-mediated AP1 trans-activation and EGF-mediated ERK activation and slight inhibition of EGF-mediated JNK activation. Taken together, these results suggest that members of the pyranone family of compounds could be developed as potential antitumor agents.

Bioprospecting from Marine Sediments of New Brunswick, Canada: Exploring the Relationship between Total Bacterial Diversity and Actinobacteria Diversity

“…Staurosporine may be responsible for the observed anti- C. albicans activity, however, as this compound does not exhibit antibacterial activity, other minor metabolites in the extract must be responsible for the VRE and MRSA activity [62]. PM050463 (an α-pyridone antibiotic) was identified as a major metabolite in 4BB9 extracts, which inhibited the growth of MRSA, VRE and C. albicans [63] Antibiotics belonging to the α-pyridone class possess diverse antimicrobial activities, thus, PM050463 is likely responsible for the observed activity. Novobiocin was isolated from 7BF3 and identified by HRMS and NMR.…”

Database on the taxonomical characterisation and potential toxigenic capacities of microorganisms used for the industrial production of food enzymes and feed additives, which do not have a recommendation for Qualified Presumption of Safety

“…bacteriocin antibacterial compound [278] pyranones antitumor [279] rebeccamycin (indolocarbazole alkaloids) antitumor [280] siderophore iron chelant [278] terpene bioactive compound [278] Streptomyces aureofaciens…”

Widespread interspecies homologous recombination reveals reticulate evolution within the genus Streptomyces

“…2). In these clusters/subclusters, multiple strains have ever been similarly identified as admixed individuals in previous Structure analyses (Andam et al, 2016;Doroghazi and Buckley, 2010) and many species are famous producers of bioactive natural compounds, such as S. albidoflavus (Seipke and Hutchings, 2013), S. albus (Schleissner et al, 2011) and S. kanamyceticus (Yanai et al, 2006), which might have benefited from the exchange of genes responsible for biosynthesis or adaptation via interspecies recombination. Moreover, several strains within these clusters/subclusters were ambiguously positioned in the network analysis with uncertain phylogenetic status (Fig.…”