A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes.

Fungal endophytes are a major source of anti-infective agents and other medically relevant compounds. However, their classical blinded-chemical investigation is a challenging process due to their highly complex chemical makeup. Thus, utilizing cheminformatics tools such as metabolomics and computer-aided modelling is of great help deal with such complexity and select the most probable bioactive candidates. In the present study, we have explored the fungal endophytes associated with the well-known antimalarial medicinal plant Artemisia annua for their production of further antimalarial agents. Based on the preliminary antimalarial screening of these endophytes and using LC-HRMS-based metabolomics and multivariate analyses, we suggested different potentially active metabolites (compounds 1-8). Further in silico investigation using the neural-network-based prediction software PASS led to the selection of a group of quinone derivatives (compounds 1-5) as the most possible active hits. Subsequent in vitro validation revealed emodin (1) and physcion (2) to be potent antimalarial candidates with IC50 values of 0.9 and 1.9 µM, respectively. Our approach in the present investigation therefore can be applied as a preliminary evaluation step in the natural products drug discovery, which in turn can facilitate the isolation of selected metabolites notably the biologically active ones.

Flavonoids from Marine-Derived Actinobacteria as Anticancer Drugs.

Flavonoids represent a large diverse group of natural products that are used as a traditional medicine against various infectious diseases. They possess many biological activities including antimicrobial, antioxidant, anti-inflammatory, anti-cancer and anti-diabetic activities. Commercially, flavonoids are mainly obtained from plants, however, several challenges are faced during their extraction. Microorganisms have been known as natural sources of a wide range of bioactive compounds including flavonoids. Actinobacteria are the most prolific group of microorganisms for the production of bioactive secondary metabolites, thus facilitating the production of flavonoids. The screening programs for bioactive compounds revealed the potential application of actinobacteria to produce flavonoids with interesting biological activities, especially anticancer activities. Since marine actinobacteria are recognized as a potential source of novel anticancer agents, they are highly expected to be potential producers of anticancer flavonoids with unusual structures and properties. In this review, we highlight the production of flavonoids by actinobacteria through classical fermentation, engineering of plant biosynthetic genes in a recombinant actinobacterium and the de novo biosynthesis approach. Through these approaches, we can control and improve the production of interesting flavonoids or their derivatives for the treatment of cancer.

Nonthermal control of Escherichia coli growth using extremely low frequency electromagnetic (ELF-EM) waves.

BACKGROUND: Escherichia coli (E. coli) bacteria normally live in the intestines of people and animals. Most E. coli are harmless and the treatment of the infection could be achieved by using antibiotics, however the effectiveness is still debatable and needs more investigation. OBJECTIVE: Researching the inhibition resonance frequency of square amplitude modulating waves (QAMW) that can inhibit the growth activity of E. coli and its ability to make division. METHODS: A range of different extremely low frequencies of square amplitude modulated waves (QAMW) from 0.1 to 1.0 Hz from two generators with a constant carrier frequency of 10 MHz, amplitude of 10 Vpp, modulating depth ± 2 Vpp and constant field strength 200 V/m were used to treat E. coli cells at 37 °C. RESULTS: The exposure of E. coli to 0.3 Hz QAMW for 90 min was the most inhibited frequency where the bacterial growth inhibited by 42.3%. Furthermore, a significant increase in antibiotic susceptibility to protein and cell wall inhibitors was investigated. Also, results of the chromosomal DNA sequences, dielectric relaxation and TEM indicated highly significant molecular and morphological changes after the exposure. CONCLUSIONS: We concluded that the exposure of E. coli to QAMW at the inhibiting frequency interfered with the bioelectric signals generated from the bacteria during the cell division and changed the cellular activity and DNA sequences, and these changes lead to a significant inhibition of the bacterial growth. This is a new promising technique that aids to avoid the repetitive use of antibiotics against the bacterial pathogens.

Transcriptomic and Ectoine Analysis of Halotolerant Nocardiopsis gilva YIM 90087T Under Salt Stress.

The genus Nocardiopsis is an unique actinobacterial group that widely distributed in hypersaline environments. In this study, we investigated the growth conditions, transcriptome analysis, production and accumulation of ectoine by Nocardiopsis gilva YIM 90087T under salt stress. The colony color of N. gilva YIM 90087T changed from yellow to white under salt stress conditions. Accumulation of ectoine and hydroxyectoine in cells was an efficient way to regulate osmotic pressure. The ectoine synthesis was studied by transferring the related genes (ectA, ectB, and ectC) to Escherichia coli. Transcriptomic analysis showed that the pathways of ABC transporters (ko02010) and glycine, serine, and threonine metabolism (ko00260) played a vital role under salt stress environment. The ectABC from N. gilva YIM 90087T was activated under the salt stress. Addition of exogenous ectoine and hydroxyectoine were helpful to protect N. gilva YIM 90087T from salt stress.