Lack of new anti-cancer and anti-infective agents directed the pharmaceutical research to natural products' discovery especially from actinomycetes as one of the major sources of bioactive compounds. Metabolomics- and dereplication-guided approach has been used successfully in chemical profiling of bioactive actinomycetes. We aimed to study the metabolomic profile of five bioactive actinomycetes to investigate the interesting metabolites responsible for their antimicrobial and anti-cancer activities. Three actinomycetes, namely, Streptomyces sp. SH8, SH10 and SH13, were found to exhibit broad spectrum of antimicrobial activities, whereas isolate SH4 showed the broadest antimicrobial activity against all tested strains. In addition, isolates SH8, SH10 and SH12 displayed potent cytotoxicity against the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), whereas isolates SH4 and SH12 exhibited potent anti-cancer activity against the hepatoma cell line hepatoma G2 (HepG2) compared with their weak inhibitory properties on the normal breast cells MCF-10A and normal liver cells transformed human liver epithelial-2 (THLE2), respectively. All bioactive isolates were molecularly identified as Streptomyces sp. via 16S rRNA gene sequencing. Our actinobacterial dereplication analysis revealed putative identification of several bioactive metabolites including tetracycline, oxytetracycline and a macrolide antibiotic, novamethymycin. Together, chemical profiling of bioactive Streptomycetes via dereplication and metabolomics helped in assigning their unique metabolites and predicting the bioactive compounds instigating their diverse bioactivities.

Literature surveys, taxonomical differences, and bioassay results have been utilized in the discovery of new natural products to aid in Actinomycetes isolate-selection. However, no or less investigation have been done on establishing the differences in metabolomic profiles of the isolated microorganisms. The study aims to utilise bioassay- and metabolomics-guided tools that included dereplication study and multivariate analysis of the NMR and mass spectral data of microbial extracts to assist the selection of isolates for scaling-up the production of antimicrobial natural products. A total of 58 actinomycetes were isolated from different soil samples collected from Ihnasia City, Egypt and screened for their antimicrobial activities against indicator strains that included Bacillus subtilis, Escherichia coli, methicillin-resistant Staphylococcus aureus and Candida albicans. A number of 25 isolates were found to be active against B. subtilis and/or to at least one of the tested indicator strains. Principal component analyses showed chemical uniqueness for four outlying bioactive actinomycetes extracts. In addition, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and dereplication study led us to further select two outlying anti-MRSA active isolates MS.REE.13 and 22 for scale-up work. MS.REE.13 and 22 exhibited zones of inhibition at 19 and 13 mm against MRSA, respectively. A metabolomics-guided approach provided the steer to target the bioactive metabolites (P<0.01) present in a crude extract or fraction even at nanogram levels but it was a challenge that such low-yielding bioactive natural products would be feasible to isolate. Validated to occur only on the active side of OPLS-DA loadings plot, the isolated compounds exhibited medium to weak antibiotic activity with MIC values between 250 and 800 μM. Two new compounds, P_24306 (C₁₀H₁₃N₂) and N_12799 (C₁₈H₃₂O₃) with MICs of 795 and 432 μM, were afforded from the scale-up of MS.REE. 13 and 22, respectively.

Marine fungi receive excessive attention as prolific producers of structurally unique secondary metabolites, offering promising potential as substitutes or conjugates for current therapeutics, whereas existing research has only scratched the surface in terms of secondary metabolite diversity and potential industrial applications as only a small share of bioactive natural products have been identified from marine-derived fungi thus far. Anthraquinones derived from filamentous fungi are a distinct large group of polyketides containing compounds which feature a common 9,10-dioxoanthracene core, while their derivatives are generated through enzymatic reactions such as methylation, oxidation, or dimerization to produce a large variety of anthraquinone derivatives. A considerable number of reported anthraquinones and their derivatives have shown significant biological activities as well as highly economical, commercial, and biomedical potentialities such as anticancer, antimicrobial, antioxidant, and anti-inflammatory activities. Accordingly, and in this context, this review comprehensively covers the state-of-art over 20 years of about 208 structurally diverse anthraquinones and their derivatives isolated from different species of marine-derived fungal genera along with their reported bioactivity wherever applicable. Also, in this manuscript, we will present in brief recent insights centred on their experimentally proved biosynthetic routes. Moreover, all reported compounds were extensively investigated for their in-silico drug-likeness and pharmacokinetics properties which intriguingly highlighted a list of 20 anthraquinone-containing compounds that could be considered as potential drug lead scaffolds.

Background: The rapid spread of antibiotic resistance has increased research interest in the discovery of natural products, mainly from actinomycetes, which have been the primary source of antimicrobial compounds. This study aimed to isolate, characterize, and optimize the production of some of the bioactive compounds from bioactive soil actinomycetes. Results: One promising soil actinomycete, which was molecularly identified as Streptomyces sp. and designated as Streptomyces sp. MS. 10, showed broad-spectrum antimicrobial activity, including activity against methicillin-resistant Staphylococcus aureus. Thus, it was selected for isolation of its major bioactive compounds. Polymerase chain reaction amplification of the genes responsible for antibiotic biosynthesis showed the presence of genes encoding type I and type II polyketide synthase. Liquid chromatography-mass spectrometry analysis found that the major antimicrobial compounds produced by Streptomyces sp. MS. 10 were weakly ionized bioactive secondary metabolites. A large-scale fermentation experiment of Streptomyces sp. MS. 10 using pre-optimized culture conditions followed by bioassay-guided chromatographic separation of its secondary metabolites resulted in the isolation of putative bioactive compounds that were identified as fatty acids using proton nuclear magnetic resonance spectroscopy. Conclusions: Egyptian soil is still a good source for exploring bioactive actinomycetes. Additionally, this study highlighted the importance of combining both physicochemical and genotypic characterization with spectroscopic analysis of the major natural products when isolating bioactive metabolites.

Background: Polycyclic aromatic hydrocarbons (PAHs) such as anthracene are one of the most toxic contaminants to our environment. Microbial biodegradation of these xenobiotics is a cost-effective technological solution. The present study aimed to recover some bacterial isolates from Beni-Suef Governorate in Egypt with high capabilities of anthracene biodegradation. The selected isolates were molecularly characterized by 16S rRNA gene sequencing, the degree of anthracene biodegradation was monitored using optical density (OD) and high-performance liquid chromatography (HPLC), PCR amplification of some selected genes encoding biodegradation of PAHs was monitored, and gas chromatography–mass spectrometry (GC–MS) analysis was applied for detecting the resulted metabolites. Result: Three bacterial isolates were studied, the 16s rRNA sequences of the isolates showed homology of the first isolate to Brevibacillus sp. (94.58 %), the second isolates showed homology to Pseudomonas sp. (94.53%) and the third isolate showed homology to Methylocystis sp. (99.61 %), all isolates showed the ability to degrade anthracene. PCR amplification of some selected genes encoding biodegradation of PAHs revealed the presence of many biodegrading genes in the selected strains. Gas chromatography-mass spectrometry (GC–MS) analysis of the metabolites resulted from anthracene biodegradation in the present study suggested that more than one biodegradation pathway was followed by the selected isolates. Conclusions: The selected strains could represent a potential bioremediation tool in solving the PAHs problem in the Egyptian environment with a clean and cost-effective technique. Graphical

The present study investigates multiple interactions of a series of marine steroids with glutathione-S-transferase (GST) and Cu–Zn human superoxide dismutase (Cu–ZnSOD) enzymes, in order to reveal insights into the process of hepatoprotection.