https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

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The re-emergence of natural products for drug discovery in the genomics era

https://cyberleninka.org/article/n/132565.pdf

Discovery and resupply of pharmacologically active plant-derived natural products: A review.

All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions.

The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics. The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics. The majority of systemic bacterial infections are caused by endogenous pathogens from human microbiota, and the opportunistic pathogen Staphylococcus aureus, commonly found in the external opening of the nostrils, is one of the most clinically important because of the prevalence of multi-drug resistant strains. The mechanisms that permit or interfere with pathogen colonization have remained unclear. This study shows that S. lugdunensis, a commensal bacterium that shares the nasal niche with S. aureus and is associated with a reduced S. aureus carriage rate in humans, produces a novel cyclic peptide antibiotic (lugdunin) that inhibits colonization by S. aureus in animal models. Lugdunin is bactericidal against major pathogens and not prone to causing development of resistance in S. aureus, suggesting that lugdunin or lugdunin-producing commensals could be valuable for preventing staphylococcal infections.

Human commensals producing a novel antibiotic impair pathogen colonization

Isochroman and isocoumarin derivatives from hypersaline lake sediment-derived fungus Penicillium sp.

Unusual octalactones from Corynespora cassiicola, an endophyte of Laguncularia racemosa

Two new metabolites from the endophytic fungus Xylaria sp. isolated from the medicinal plant Curcuma xanthorrhiza

Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium , yielded a new tryptophan derived alkaloid, 3-((1-hydroxy-3-(2-methylbut-3-en-2-yl)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[ e ][1,4]diazepine-2,5-dione ( 1 ), and a new meroterpenoid, austalide R ( 2 ), together with three known compounds ( 3 – 5 ). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and two-dimensional NMR ( 1 H, 13 C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y.

Amal H. Aly

Papers

Isochroman and isocoumarin derivatives from hypersaline lake sediment-derived fungus Penicillium sp.

Unusual octalactones from Corynespora cassiicola, an endophyte of Laguncularia racemosa

Two new metabolites from the endophytic fungus Xylaria sp. isolated from the medicinal plant Curcuma xanthorrhiza

Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

Marine Bacterial Inhibitors from the Sponge-Derived Fungus Aspergillus sp.