Source Of Natural Products Research Articles

Metagenomic and metatranscriptomic exploration of the Egyptian Red Sea sponge Theonella sp. associated microbial community.

Marine sponges associated microorganisms are considered to be prolific source of bioactive natural products. Omics-based techniques such as metagenomics and metatranscriptomics have been used as effective tools to discover natural products. In this study, we used integrated metagenomic and metatranscriptomic analysis of three samples of the Egyptian Red Sea sponge Theonella sp. microbiome to obtain a complete picture of its biosynthetic activity to produce bioactive compounds. Our data revealed high biodiversity of the Egyptian sponge microbiota represented by 38 bacterial phyla with Candidate Phylum Poribacteria as the most abundant phyla with an average of 27.5% of the microbial community. The analysis also revealed high biosynthetic activity of the sponge microbiome through detecting different types of biosynthetic gene clusters (BGCs) with predicted antibacterial, cytotoxic and inhibitory bioactivity and the majority of these clusters were found to be actively transcribed. The complete BGCs of the cytotoxic theonellamide and misakinolide were detected and found to be actively transcribed. The majority of the detected BGCs were predicted to be novel as they did not show any similarity with any known cluster in the MIBiG database.

Comparative LC-MS/MS-based molecular networking, DNA fingerprinting, and in vitro anti-Helicobacter pylori activity of three Egyptian Ficus cultivars

Ficus species (Moraceae) have been used for nutrition and traditional medicine, and plants from this family are phytochemically abundant and serve as a potential source of natural products. As a result of the inherent complexity of the plant metabolomes and the fact that these Ficus species chemical space has not yet been fully decoded, it is still difficult to characterize their phytochemistry. Therefore, this study, we suggest the use of the molecular networking to elucidate the chemical classes existing in leaves of three Ficus species (F. deltoidei Jack, F. drupacea Thunb and F. sycomorus L.) and highlight the importance of molecular networking in examining their chemotaxonomy . By using computational tools, 90 metabolites were annotated , including phenolic acids, flavonoids, furanocoumarins, fatty acids and terpenoids. Phenolic acids were detected as the main class present in the three studied species. Flavonoids-C-glycosides, flavonoids-O-glycosides and isoflavonoids were mainly present in F. drupacea and F. sycomorus, while furanocoumarins were proposed in F. sycomorus. Vomifoliol-based sesquiterpenes were proposed in F. deltoidei. The chemotaxonomic differentiation agreed with the DNA fingerprinting using SCOT and ISSR markers. F. deltoidei, in particular, had a divergent chemical fingerprint as well as a different genotype. Chemotype differentiation using chemical fingerprints, in conjunction with the proposed genetic markers, creates an effective identification tool for the quality control of the raw materials and products derived from those three Ficus species. As well, F. drupacea exploited the most potent inhibition of H. pylori with MIC of 7.81 µg/ mL compared with clarithromycin. Overall, molecular networking provides a promising approach for the exploration of the chemical space of plant metabolomes and the elucidation of chemotaxonomy.

Isolation and characterization of dihydropyran-ring containing meroterpenoids from Ganoderma lucidum and their inhibitory activity against renal fibrosis-related protein expression

The Ganoderma lucidum mushroom, which has been used as a traditional medicine in China for more than 2000 years, is a source of many interesting natural product. In this study, the five undescribed minor meroterpenoids baoslingzhines F–J (1−5), containing a dihydropyran moiety, were isolated as racemic mixtures from the fruiting bodies of G. lucidum. These substances were structurally and stereochemically characterized by using spectroscopic and computational methods. Chiral HPLC was employed to separate the (+)- and (−)-antipodes. A survey of the activities against kidney fibrosis showed that both enantiomers of baoslingzhines F–J inhibit expression of renal fibrosis-related proteins, including fibronectin, collagen I and ɑ-SMA in TGF-β1-induced rat kidney proximal tubular cells.

Screening Amazon rainforest plant extracts for antimicrobial activity: a 15-year commitment to the Brazilian biodiversity

IntroductionThe need for new tools to treat infections is constantly growing due to the possibilities of emerging diseases related to environmental changes, climatic catastrophes, microorganism resistance, and human and animal aging, leading to an evident unbalance in the planet’s health. Brazil contains the most significant portion of world biodiversity, a potential source of new antimicrobial natural products. Nonetheless, its environment, particularly its forests, and rainforests, is under threat, meaning that rapidly conducted, comprehensive research into the potential of antimicrobial activity to address this threat is urgently needed.MethodsIn this study, plants from the Amazon rainforest and the Atlantic forests were collected and tested against several pathogenic microbes relevant to humans, animals, and the environment, and subjected to large-scale susceptibility assays, bioautography, and Artemia salina toxicity assays. From the plants, 2,280 organic and aqueous extracts were obtained from different organs, namely leaves, barks, flowers, fruits, and seeds, and subjected to a large-scale susceptibility screening assay against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus mutans, Streptococcus sanguinis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia pachydermatis, Malassezia furfur, and Listeria monocytogenes. Results and discussionThe selected extracts were subjected to antimicrobial susceptibility tests to determine their inhibition zone diameters and minimum bactericidal concentrations, to bioautography, and to an Artemia salina toxicity assay, which resulted in 154 active extracts. Moreover, 111 out of 154 extracts were ranked based on scores established by the p-values and the mean rank differences in each set of test results. The final ranking identified which extracts should be studied in further phytochemical research using thin-layer chromatography techniques as a priority. The extracts obtained from plants belonging to Combretaceae, Connaraceae, Convolvulaceae, Fabaceae, Malpighiaceae, Moraceae, Piperaceae, Polygonaceae, and Salicaceae were selected as the most promising ones and used to support the identification of plant-based antimicrobial active compounds from the immense biodiversity of Brazilian forests.

New Olimycins from a Cold-Seep-Derived Streptomyces olivaceus.

Cold-seeps are areas of the ocean floor in which hydrogen sulfide and methane are released into the open water. The cold-seep microbes are an emerging source of novel bioactive natural products. Four new ansa-ring opened linear ansamycin analogues, named olimycins E-H (1-4) were isolated from the cold-seep-derived Streptomyces olivaceus OUCLQ19-3. The planar and stereochemical structures of the isolated compounds were elucidated based on extensive MS and NMR spectroscopic analyses together with ECD calculations.

Antiproliferative, Antioxidant, Chemopreventive and Antiangiogenic Potential of Chromatographic Fractions from Anemonia sulcata with and without Its Symbiont Symbiodinium in Colorectal Cancer Therapy.

Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.

Evaluation of Tamarix nilotica Fractions in Combating Candida albicans Infections

ABSTRACT Objectives Evaluation of the antifungal properties of Tamarix nilotica fractions against Candida albicans clinical isolates. Methods The in vitro antifungal potential was evaluated by agar well diffusion and broth microdilution methods. The antibiofilm potential was assessed by crystal violet, scanning electron microscopy (SEM), and qRT-PCR. The in vivo antifungal activity was evaluated by determining the burden in the lung tissues of infected mice, histopathological, immunohistochemical studies, and ELISA. Results Both the dichloromethane (DCM) and ethyl acetate (EtOAc) fractions had minimum inhibitory concentration (MIC) values of 64–256 and 128–1024 μg/mL, respectively. SEM examination showed that the DCM fraction decreased the biofilm formation capacity of the treated isolates. A significant decline in biofilm gene expression was observed in 33.33% of the DCM-treated isolates. A considerable decline in the CFU/g lung count in infected mice was observed, and histopathological examinations revealed that the DCM fraction maintained the lung tissue architecture. Immunohistochemical investigations indicated that the DCM fraction significantly (p < 0.05) decreased the expression of pro-inflammatory and inflammatory cytokines (TNF-α, NF-kB, COX-2, IL-6, and IL-1β) in the immunostained lung sections. The phytochemical profiling of DCM and EtOAc fractions was performed using Liquid chromatography-mass spectrometry (LC-ESI-MS/MS). Conclusion T. nilotica DCM fraction could be a significant source of natural products with antifungal activity against C. albicans infections.

Herbal medicine and its impact on the gut microbiota in colorectal cancer.

It is well-established that there are trillions of gut microbiota (GM) in the human gut. GM and its metabolites can reportedly cause cancer by causing abnormal immune responses. With the development of sequencing technology and the application of germ-free models in recent years, significant inroads have been achieved in research on GM and microbiota-related metabolites. Accordingly, the role and mechanism of GM in colorectal cancer (CRC) development have been gradually revealed. Traditional Chinese medicine (TCM) represents an important source of natural medicines and herbal products, with huge potential as anti-CRC agents. The potential application of TCM to target gut microbes for the treatment of colorectal cancer represents an exciting area of investigation.

Anti-cervical cancer potentials and GC-MS analysis of Cymbopogon citratus (DC.) Stapf and Origanum vulgare Linn.Extracts

Cervical cancer is the fourth leading cause of death among women worldwide and many conventional drugs have several side effects and poor selectivity in cancer treatment. In this study, the cytotoxic potentials of C. citratus(CC) and O. vulgare(OV) extracts were assessed as a probable source of natural products for the treatment of cervical cancer. The crude extracts and fractions were challenged against cervical (HeLa) cancer cell line using MTT assay. The phytochemical components present in the extracts were analyzed using gas chromatography-mass spectrometry (GC-MS).The CC crude exhibited the highest inhibition on the growth of HeLa (CC50=43.43±0.05 µg/mL) as compared with OV crude (170.2±0.11 µg/mL). The CC fractions’ potentials were in the order of n-hexane (3.81±0.22 µg/mL) ˃dichloromethane (DCM) (5.44±0.16 µg/mL)˃aqueous (38.57±0.12 µg/mL)˃ethylacetate (50.24±0.05 µg/mL). Similarly, OV fractions’ potentials were in the order of n-hexane (57.95±0.12 µg/mL)˃DCM (61.63±0.07 µg/mL)˃ethylacetate (172.4±0.21 µg/mL)˃aqueous (176±0.14 µg/mL).These results were compared with vincristine (standard) with aCC50 value of 0.75±0.14 µg/mL.The major compounds present in CC aqueous extract with their percentage composition includeCyclohexasiloxane,dodecamethyl-(20.79%),Cycloheptasiloxane,tetradecamethyl-(17.93%), Cyclopentasiloxane, decamethyl-(15.04%), Cyclooctasiloxane, hexadecamethyl-(8.98%). OV aqueous extract revealed Hexadecanoic acid, methyl ester(24.71%), 9-Octadecenoic acid (Z)-, methyl ester(22.52%), Methyl stearate(15.40%), 9-Octadecenoic acid (Z)-, methyl ester(11.56%), as its major compounds.Our results suggest that the CC and OV plants are a favorable source of natural products with promising properties for anti-cervical drug discovery.

Isolation and Biological Activity of Iezoside and Iezoside B, SERCA Inhibitors from Floridian Marine Cyanobacteria.

Marine cyanobacteria are a rich source of bioactive natural products. Here, we report the isolation and structure elucidation of the previously reported iezoside (1) and its C-31 O-demethyl analogue, iezoside B (2), from a cyanobacterial assemblage collected at Loggerhead Key in the Dry Tortugas, Florida. The two compounds have a unique skeleton comprised of a peptide, a polyketide and a modified sugar unit. The compounds were tested for cytotoxicity and effects on intracellular calcium. Both compounds exhibited cytotoxic activity with an IC50 of 1.5 and 3.0 μΜ, respectively, against A549 lung carcinoma epithelial cells and 1.0 and 2.4 μΜ against HeLa cervical cancer cells, respectively. In the same cell lines, compounds 1 and 2 show an increase in cytosolic calcium with approximate EC50 values of 0.3 and 0.6 μΜ in A549 cells and 0.1 and 0.5 μΜ, respectively, in HeLa cells, near the IC50 for cell viability, suggesting that the increase in cytosolic calcium is functionally related to the cytotoxicity of the compounds and consistent with their activity as SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) inhibitors. The structure-activity relationship provides evidence that structural changes in the sugar unit may be tolerated, and the activity is tunable. This finding has implications for future analogue synthesis and target interaction studies.

Microbial Endophytes: Emerging Trends and Biotechnological Applications.

A plethora of knowledge on the role of endophytic microorganisms has been reported in recent years. The cooperative chemistry between the endophytes and the internal host tissue has turned them into a crucial aid for biotechnological applications. Microbial endophytes are ubiquitous among most plant species on earth and contribute to the benefit of host plants by generating a wide range of metabolites that provide the plant with survival value. Endophytes can either directly stimulate plant growth by producing phytohormones or indirectly stimulate plant growth by increasing the availability of soil nutrients to plants. Endophytes may also help suppress diseases in plants directly by neutralizing environmental toxic elements, and by inhibiting plant pathogens by antagonistic action, or indirectly by stimulating induced plant systemic resistance. Several natural compounds produced by endophytes as secondary metabolites are beneficial to both plants and humans. This is why endophytes are regarded as a significant source of novel natural products of value in modern medicine, agriculture, and industry. Endophytes are known for producing pigments, bioactive compounds, and industrially important enzymes, like glucanase, amylase, laccase, etc. Some endophytes can also produce nanoparticles that potentially have numerous applications in a variety of fields. They also play an important role in biodegradation and bioremediation, both of which are beneficial to the environment and ecology. In this review, we highlighted potential biotechnological applications of endophytic microbes, as well as their diverse importance in plant growth and public health.

Understanding Autologous Spliceostatin Transcriptional Regulation to Derive Parts for Heterologous Expression in a Burkholderia Bacterial Host.

Burkholderia β-Proteobacteria are emerging sources of natural products. We are interested in developing Burkholderia sp. FERM BP-3421 into a synthetic biology chassis to facilitate natural product discovery. FERM BP-3421 produces autologous spliceostatins on gram per liter scale. We reasoned that transcription factors and promoters that regulate spliceostatin biosynthesis would provide valuable parts for heterologous expression. Herein we demonstrate that fr9A encodes a pathway-specific transcriptional activator of spliceostatin biosynthesis. In-frame deletion of fr9A abolished spliceostatin production, which was restored by genetic complementation. Using transcriptomics and green fluorescent protein (GFP) reporter assays, we identified four fr9 promoters, three of which are activated by LuxR-type regulator Fr9A. We then constructed an Fr9A-regulated promoter system that was compared to benchmarks and effectively applied for GFP and capistruin lasso peptide expression in an optimized host background. Our findings enrich the genetic toolbox for optimizing heterologous expression and promoting the discovery and development of natural products from Burkholderia bacteria.

Volatile Compounds and Biological Activity of the Essential Oil of Aloysia citrodora Paláu: Comparison of Hydrodistillation and Microwave-Assisted Hydrodistillation.

Aromatic plants are a remarkable source of natural products. Aloysia citrodora Paláu (Verbenaceae), commonly known as lemon verbena, is a relevant source of essential oils with potential applications due to its lemony scent and bioactive properties. Studies carried out on this species have focused on the volatile composition of the essential oil obtained by Clevenger hydrodistillation (CHD), with little information available on alternative extraction methodologies or the biological properties of the oil. Therefore, this work aimed to compare the volatile composition, antioxidant activity, cytotoxicity, anti-inflammatory and antibacterial activities of the essential oil extracted by conventional hydrodistillation by Clevenger (CHD) and Microwave-Assisted Hydrodistillation (MAHD). Significant differences (p < 0.05) were observed for some compounds, including the two major ones, geranial (18.7-21.1%) and neral (15.3-16.2%). Better antioxidant activity was exhibited by the MAHD essential oil in DPPH radical scavenging and reducing power assays, while no differences were observed in the cellular antioxidant assay. The MADH essential oil also presented higher inhibition against four tumoral cell lines and exhibited lower cytotoxicity in non-tumoral cells as compared with Clevenger-extracted essential oil. In contrast, the latter showed higher anti-inflammatory activity. Both essential oils were able to inhibit the growth of eleven out of the fifteen bacterial strains tested.

Plant Extracts as a Source of Natural Products with Potential Antimalarial Effects: An Update from 2018 to 2022.

Malaria kills more than 500,000 people yearly, mainly affecting Africa and Southeast Asia. The disease is caused by the protozoan parasite from the genus Plasmodium, with Plasmodium vivax and Plasmodium falciparum being the main species that cause the disease in humans. Although substantial progress has been observed in malaria research in the last years, the threat of the spread of Plasmodium parasites persists. Artemisinin-resistant strains of this parasite have been reported mainly in Southeast Asia, highlighting the urgent need to develop more effective and safe antimalarial drugs. In this context, natural sources, mainly from flora, remain underexplored antimalarial spaces. The present mini-review explores this space focusing on plant extracts and some of their isolated natural products with at least in vitro antiplasmodial effects reported in the literature comprising the last five years (2018-2022).

Comparative genome features and secondary metabolite biosynthetic potential of Kutzneria chonburiensis and other species of the genus Kutzneria

Actinobacteria are well known as a rich source of diversity of bioactive secondary metabolites. Kutzneria, a rare actinobacteria belonging to the family Pseudonocardiaceae has abundance of secondary metabolite biosynthetic gene clusters (BGCs) and is one of important source of natural products and worthy of priority investigation. Currently, Kutzneria chonburiensis SMC256T has been the latest type-strain of the genus and its genome sequence has not been reported yet. Therefore, we present the first report of new complete genome sequence of SMC256T (genome size of 10.4 Mbp) with genome annotation and feature comparison between SMC256T and other publicly available Kutzneria species. The results from comparative and functional genomic analyses regarding the phylogenomic and the clusters of orthologous groups of proteins (COGs) analyses indicated that SMC256T is most closely related to Kutzneria sp. 744, Kutzneria kofuensis, Kutzneria sp. CA-103260 and Kutzneria buriramensis. Furthermore, a total of 322 BGCs were also detected and showed diversity among the Kutzneria genomes. Out of which, 38 clusters showing the best hit to the most known BGCs were predicted in the SMC256Tgenome. We observed that six clusters responsible for biosynthesis of antimicrobials/antitumor metabolites were strain-specific in Kutzneria chonburiensis. These putative metabolites include virginiamycin S1, lysolipin I, esmeraldin, rakicidin, aclacinomycin and streptoseomycin. Based on these findings, the genome of Kutzneria chonburiensis contains distinct and unidentified BGCs different from other members of the genus, and the use of integrative genomic-based approach would be a useful alternative effort to target, isolate and identify putative and undiscovered secondary metabolites suspected to have new and/or specific bioactivity in the Kutzneria.

New secondary metabolites produced by Paraphoma radicina FB55 as potential antifungal agents.

Microorganisms in specific environments are rich sources of bioactive natural products as they produce compounds that can aid their survival in harsh environments. In an effort to investigate antifungal compounds produced by microorganisms, the fungal strain Paraphoma radicia FB55, isolated from a marine sediment of the Beaufort Sea, north of Alaska, was subjected to chemical investigation. Chromatography of the culture extracts yielded two new compounds (1 and 2) and eight known compounds (3-10). Their structures were determined using spectroscopic and chemical methods. Compound 1 was a new analog of the known compound (3) with an isobenzofuranone skeleton. The absolute configuration of the chiral center in 1 was established by comparison of its ECD and specific rotation values with those for a known analogue. Compound 2 is a polyketide-amino acid hybrid. Comprehensive Nuclear Magnetic Resonance (NMR) analysis indicated that 2 consisted of two substructures:5-methyl-6-oxo-2,4-heptadienoic acid and isoleucinol. The absolute configuration of the isoleucinol moiety in 2 was determined to be D using Marfey's method. All the isolated compounds were evaluated for antifungal activities. Although the antifungal activity of the isolated compounds was not potent, co-treatment of compounds 7 and 8 with a clinically available amphotericin B (AmB) lowered the IC50 values of AmB by synergism against human pathogenic yeast.

Potential antioxidative components from Syringa oblata Lindl stems revealed by affinity ultrafiltration with multiple drug targets

Traditional Chinese medicine is the main source of natural products due to its remarkable clinical efficacy. Syringa oblata Lindl (S. oblata) was widely used because of its extensive biological activities. However, to explore the antioxidant components of S. oblata against tyrosinase, the experiments of antioxidation in vitro were employed. At the same time, the determination of TPC was also use to assess the antioxidant ability of CE, MC, EA and WA fractions and the liver protective activity of the EA fraction was evaluated by mice in vivo. Next, UF-LC-MS technology was performed to screen and identify the efficient tyrosinase inhibitors in S. oblata. The results showed that alashinol (G), dihydrocubebin, syripinin E and secoisolariciresinol were characterized as potential tyrosinase ligands and their RBA values were 2.35, 1.97, 1.91 and 1.61, respectively. Moreover, these four ligands can effectively dock with tyrosinase molecules, with binding energies (BEs) ranging from 0.74 to −0.73 kcal/mol. In addition, tyrosinase inhibition experiment was employed to evaluate the tyrosinase inhibition activities of four potential ligands, the result showed that compound 12 (alashinol G, IC50 = 0.91 ± 0.20 mM) showed the strongest activity to tyrosinase, followed by secoisolariciresinol (IC50 = 0.99 ± 0.07 mM), dihydrocubebin (IC50 = 1.04 ± 0.30 mM) and syripinin E (IC50 = 1.28 ± 0.23 mM), respectively. The results demonstrate that S. oblata might have excellent antioxidant activity, and UF-LC-MS technique is a effective means to filter out tyrosinase inhibitors from natural products.

Alternaria alternata (SDHY01/02), a fungus associated with Lamellodysidea herbacea: its anticancer potential and responsible constituent(s).

One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC50 ≤ 20µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC50 values ≤ 20µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC50 values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC50 4.27µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternatacan be exploited to get anticancer molecule(s) in the future.

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.

Due to the continued emergence of resistance and a lack of new and promising antibiotics, bacterial infection has become a major public threat. High-throughput screening (HTS) allows rapid screening of a large collection of molecules for bioactivity testing and holds promise in antibacterial drug discovery. More than 50% of the antibiotics that are currently available on the market are derived from natural products. However, with the easily discoverable antibiotics being found, finding new antibiotics from natural sources has seen limited success. Finding new natural sources for antibacterial activity testing has also proven to be challenging. In addition to exploring new sources of natural products and synthetic biology, omics technology helped to study the biosynthetic machinery of existing natural sources enabling the construction of unnatural synthesizers of bioactive molecules and the identification of molecular targets of antibacterial agents. On the other hand, newer and smarter strategies have been continuously pursued to screen synthetic molecule libraries for new antibiotics and new druggable targets. Biomimetic conditions are explored to mimic the real infection model to better study the ligand-target interaction to enable the designing of more effective antibacterial drugs. This narrative review describes various traditional and contemporaneous approaches of high-throughput screening of natural products and synthetic molecule libraries for antibacterial drug discovery. It further discusses critical factors for HTS assay design, makes a general recommendation, and discusses possible alternatives to traditional HTS of natural products and synthetic molecule libraries for antibacterial drug discovery.

Biocontrol Potential of Novel Borrelidin-Producing &lt;i&gt;Streptomyces rochei&lt;/i&gt; 3IZ-6 Isolated from Izraeli Soil

The soil actinobiota of various climatic zones are a rich source of bioactive natural products, including novel drugs. A complex of soil actinomycetes in the upper horizon of the grumusols (Vertisols) on the western coast of Lake Kinneret in the vicinity of Tiberias (Lower Galilee, Israel) was studied. The screening of the antagonistic activity of 26 isolates using on a dual reporter system revealed the bacterial strain 3IZ-6, which had the ability to inhibit protein synthesis. Strain 3IZ-6 was assigned to Streptomyces rochei by polyphase taxonomy approach. The active substance of S. rochei 3IZ-6 was isolated and purified using solid-phase extraction and HPLC. Toe-print analysis and mass spectrometry data allowed to establish, that active compound is a known inhibitor of protein biosynthesis, borrelidin. S. rochei 3IZ-6 can be used as a producer of borrelidin in biocontrol against phytopathogens and weeds.