Discovery Of Novel Bioactive Compounds Research Articles

Phytochemical characterisation of leaves and stems of Murraya koenigii (L.) Sprengel and Murraya paniculata (L.) Jack and their antibacterial activity against multidrug‐resistant Acinetobacter baumannii bacterial infection

SummaryAntibiotic resistance is now deemed a worldwide problem that puts public health at risk. The potential of Murraya (Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq.) leaves and stems as antibacterial agents against multidrug‐resistant Acinetobacter baumannii (MDRAB) was assessed in our study. First, screening was performed by disc diffusion assay, and minimum inhibitory concentration values were then determined as compared to tigecycline. A. baumnii mouse model of infection was established to substantiate the antibacterial activity of Murraya species. Results revealed high antimicrobial activity for stem of both plants where leaves showed moderate to weak activity. Phytochemical characterisation revealed the identification of 129 metabolites belonging to different classes of compounds viz. coumarins, carbazole alkaloids, flavonoids, phenolic acids, and miscellaneous. In vivo data from the animal model supported the high efficiency of M. paniculata stems as promising extract for lead candidates against MDRAB pulmonary infections. Inhibition of its essential MurF (UDP‐N‐acetylmuramoyl‐tripeptide‐D‐alanyl‐d‐alanine ligase) protein has been reported as a potential target for broad‐spectrum drugs. In silico results after molecular docking to MurF from Acinetobacter baumannii (PDB ID: 4QF5) showed competitive binding mode to ATP ligand at the active site predicting antibacterial activity of the tested compounds. Furthermore, chlorogenic acid, caffeic acid, sinapic acid, feruloyl agmatine, and mahanimbidine were detected as the key discriminatory metabolites correlated with antibacterial activity. To our knowledge, this is the first in vivo anti‐MDRAB study for the investigated plant. Murraya plants have enormous possibility for the discovery of novel bioactive compounds which could combat against resistant microorganisms.

Effect of n-Hexane Extract from Tanacetum argenteum (Lam.) Willd. subsp. argenteum on the Secretion of Proinflammatory Cytokines in THP-1 Cell Line

Inflammation is an initial biological process that involves the activation of the immune system in response to injury, infection or exposure to toxic agents. During this process, cytokines, small proteins produced by immune cells, play a vital role in regulating the immune response. Inflammatory cytokines, including interleukins, tumor necrosis factor-α, nitric oxide, and interferon-gamma, initiate the immune response and promote inflammation. Natural products are frequently a source of potential anti-inflammatory compounds, and screening natural products can lead to the discovery of novel bioactive compounds. The present study aimed to investigate the effects of n-hexane extract from Tanacetum argenteum subsp. argenteum on the lipopolysaccharide-induced inflammatory response in human macrophages THP-1 cell. Cells were incubated with different concentrations of n-hexane extract, and the inhibitor effects of the extract exposure on various cytokine secretions were determined. The findings demonstrated that n-hexane extract dramatically decreased the levels of interleukin‑6, interleukin‑1β, and tumor necrosis factor‑α in differentiated THP-1 cells, indicating the remarkable anti-inflammatory potential of the extract. Furthermore, in silico analysis of toxicogenomic data revealed the interactions between the active component of the n-hexane extract and interleukin-6, interleukin-1β, and tumor necrosis factor.

Unlocking the potential of bacterial endophytes from medicinal plants for drug discovery.

Among the plant-associated microorganisms, the so-called endophytes continue to attract much attention because of their ability not only to protect host plants from biotic and abiotic stress factors, but also the potential to produce bioactive secondary metabolites. The latter property can elicit growth-promoting effects on plants, as well as boost the production of plant-specific secondary metabolites with valuable pharmacological properties. In addition, endophyte-derived secondary metabolites may be a rich source for the discovery of drugs to treat various diseases, including infections and cancer. However, the full potential of endophytes to produce bioactive secondary metabolites is often not revealed upon conventional cultivation in the laboratory. New advances in genomics and metabolic engineering offer exciting opportunities for the exploration and exploitation of endophytes' biosynthetic potential. This review focuses on bacterial endophytes of medicinal plants, some of their secondary metabolites and recent advances in deciphering their biosynthesis. The latter may assist in genetic engineering efforts aimed at the discovery of novel bioactive compounds with the potential to be developed into drugs.

Review on phytochemical constituents and pharmacological activities of genus Galium

Medicinal plants are a rich source of phytochemical constituents of diverse structures that are behind their various pharmacological effects. Plants of genus Galium named Bedstraws, family Rubiaceae, are distributed throughout North and South America, Europe, the northern U.S., southern Canada, and tropical Asia. More than 600 species have been used in traditional medicine for treating different ailments. Owing to the valuable published uses of these plant species, and the versatility of their bioactive metabolites such as Galium verum, Galium aparine, Galium mollugo, and G. odoratum, it was deemed interesting to summarize the previous studies done on this genus to discuss the pharmacological profile of all isolated classes of metabolites. The search was adopted using some essential keywords such as Galium, phytochemistry, pharmacology, and biological activity from journals and books in databases such as Scopus, Elton B. Stephens CO, ScienceDirect, Embase, security identifier, and Medline from 1995 to 2024. The results showed that species belonging to Galium have various pharmacological activities including antimicrobial, antioxidant, anti-cancer, immunomodulatory, and anti-inflammatory effects because they are rich in phenolic compounds, iridoid glycosides, anthraquinones, phytosterols, saponins, and essential oils. Accordingly, this review will stimulate the scientific community for further research and boost the discovery of novel bioactive compounds from various species belonging to this genus distributed worldwide.

Apoptotic and Autophagic Cell Death Effects of the Hexane Extract of Tropical Marine Algae Halymenia durvillei against Human Glioblastoma Cells: In vitro and in silico Studies

Glioblastoma (GBM) considered as aggressive brain cancer with high mortality rate in patients even after surgical resection. Resistant to chemotherapy is the major problem in GBM therapy. Discovery of novel bioactive compounds from algae is being investigated as alternative sources for potential treatment as well as prevention in glioblastoma. This study revealed the effects of marine red algae extract from hexane solvent fraction of Halymenia durvillei (HDHE) on proliferation and cell death in A172 human GBM cells. HDHE decreased proliferation and promoted cell cycle arrest at G2/M phase. HDHE induced apoptotic cell death in A172 cells through mitochondrial membrane dysfunction, the decrease of anti-apoptotic Bcl-2 protein expression, and activation of caspase 3/7. Moreover, HDHE increased intracellular reactive oxygen species (ROS) production and accumulation of LC3-II, an autophagic marker. The docked conformation of palmitic acid, a major component of HDHE, showed a high affinity binding to TP53 and Beclin-1 as cell death-related target molecules. This research conclusively demonstrated that HDHE might serve as a potent anticancer agent against glioblastoma by promoting apoptotic and autophagic cell death in A172 human GBM cells. HIGHLIGHTS The palmitic acid-enriched extract of red alga Halymenia durvillei (HDHE) could inhibit proliferation of A172 human glioblastoma cells by arresting cell cycle at G2/M phase HDHE could induce both caspase-dependent apoptotic and autophagic death of A172 cells Palmitic acid, a major component of HDHE, showed a high affinity binding to TP53 and Beclin-1 The extract could be beneficial to develop as chemopreventive agents or food supplements against glioblastoma GRAPHICAL ABSTRACT

Antibacterial activity of two actinomycetes species isolated from black sand in North Egypt

Increasingly high levels of multidrug-resistant (MDR) pathogens have necessitated the discovery of novel bioactive compounds. For this reason, two actinomycetes strains, Streptomyces griseorubens and Streptomyces rochei, were isolated for the first time from the black sand shores of Kafr El Sheikh in Egypt, which is home to several large fish farms. Isolates were identified via phenotypic, biochemical and 16S rRNA sequence protocols. Both strains exhibited powerful antimicrobial activity against three serious MDR pathogens: Bacillus subtilis, Salmonella enteritidis and Pseudomonas aeruginosa. The bioactive compounds of isolates’ filtrates were identified using gas chromatography–mass spectroscopy (GC-MS). For S. griseorubens, the detectable antibacterial compounds were hexanoic acid, 2-ethyl-, 2-ethylhexyl ester, n-Decane, hexadecanoic acid methyl ester, benzene acetic acid, ricinolic acid, and ethylparaben, while S. rochei secretes heptadecane, 2,6-dimethyl-, benzene acetic acid, dibutyl phthalate, octacosane, hexacosane, and vitamin A aldehyde. These results strongly encourage the use of these eco-friendly isolates as a biocontrol against MDR pathogens that attack fish farms. Significance: Streptomyces spp. act as strong weapons for fighting multidrug resistance in pathogenic bacteria – one of the most important current threats to public health. They are additionally regarded as eco-friendly organisms that can be used as a biocontrol agent against infections that endanger fish farms.

Genome Mining of a Novel Marine Sponge Symbiont Nocardia sp. BML-15-R-026U Reveals High Biosynthetic Potential for Secondary Metabolites, Including a Non-Ribosomal Peptide and a Polyketide of High Novelty

Antibiotic and drug resistance poses serious global public health threats, leading to substantial infections and fatalities annually. Addressing these issues requires the discovery of novel bioactive compounds and a faster and more cost-effective discovery process. However, traditional approaches, which require isolation and multi-step purification of compounds from organisms and running of initial assays, suffer from serious limitations such asthe need for substantial amounts of biological material and high rates of compound rediscoveries. Because the biosynthetic capabilities of organisms are encoded in their genomes, genome mining provides a promising solution that would complement traditional approaches. This study conducted long-read whole genome sequencing on a marine sponge symbiont, Nocardia sp. BML-15-R-026U, to explore its genomic repertoire of secondary metabolite-encoding Biosynthetic Gene Clusters (BGCs). A four-contig genome assembly was generated for this isolate with a high degree of completeness and an estimated genome size of 4.84 Mbp. Its genome displays remarkable biosynthetic potential by containing at least 34 distinct secondary metabolite BGCs, predominantly Non-Ribosomal Peptide Synthetase (NRPS) and Polyketide Synthase (PKS) systems capable of producing novel chemical structures. Further analysis was focused on two genomic regions. In region 3.10, the study predicted a BGC for a novel, serine-rich non-ribosomal peptide with a predicted molecular weight of 2754 g/mol. Region 3.12 contained an iterative type-I PKS BGC, suggesting the potential synthesis of a polyketide compound with oxidoreductase-inhibiting properties. This study highlights genome mining as a productive early-phase approach for identifying promising drug leads and has identified the most promising candidates among this isolate’s BGCs for experimental validation

Genome mining reveals novel biosynthetic gene clusters in entomopathogenic bacteria

The discovery of novel bioactive compounds produced by microorganisms holds significant potential for the development of therapeutics and agrochemicals. In this study, we conducted genome mining to explore the biosynthetic potential of entomopathogenic bacteria belonging to the genera Xenorhabdus and Photorhabdus. By utilizing next-generation sequencing and bioinformatics tools, we identified novel biosynthetic gene clusters (BGCs) in the genomes of the bacteria, specifically plu00736 and plu00747. These clusters were identified as unidentified non-ribosomal peptide synthetase (NRPS) and unidentified type I polyketide synthase (T1PKS) clusters. These BGCs exhibited unique genetic architecture and encoded several putative enzymes and regulatory elements, suggesting its involvement in the synthesis of bioactive secondary metabolites. Furthermore, comparative genome analysis revealed that these BGCs were distinct from previously characterized gene clusters, indicating the potential for the production of novel compounds. Our findings highlighted the importance of genome mining as a powerful approach for the discovery of biosynthetic gene clusters and the identification of novel bioactive compounds. Further investigations involving expression studies and functional characterization of the identified BGCs will provide valuable insights into the biosynthesis and potential applications of these bioactive compounds.

Advances and Challenges in CRISPR/Cas-Based Fungal Genome Engineering for Secondary Metabolite Production: A Review.

Fungi represent an important source of bioactive secondary metabolites (SMs), which have wide applications in many fields, including medicine, agriculture, human health, and many other industries. The genes involved in SM biosynthesis are usually clustered adjacent to each other into a region known as a biosynthetic gene cluster (BGC). The recent advent of a diversity of genetic and genomic technologies has facilitated the identification of many cryptic or uncharacterized BGCs and their associated SMs. However, there are still many challenges that hamper the broader exploration of industrially important secondary metabolites. The recent advanced CRISPR/Cas system has revolutionized fungal genetic engineering and enabled the discovery of novel bioactive compounds. In this review, we firstly introduce fungal BGCs and their relationships with associated SMs, followed by a brief summary of the conventional strategies for fungal genetic engineering. Next, we introduce a range of state-of-the-art CRISPR/Cas-based tools that have been developed and review recent applications of these methods in fungi for research on the biosynthesis of SMs. Finally, the challenges and limitations of these CRISPR/Cas-based systems are discussed and directions for future research are proposed in order to expand their applications and improve efficiency for fungal genetic engineering.

Tapping into Plant-Microbiome Interactions through the Lens of Multi-Omics Techniques.

This review highlights the pivotal role of root exudates in the rhizosphere, especially the interactions between plants and microbes and between plants and plants. Root exudates determine soil nutrient mobilization, plant nutritional status, and the communication of plant roots with microbes. Root exudates contain diverse specialized signaling metabolites (primary and secondary). The spatial behavior of these metabolites around the root zone strongly influences rhizosphere microorganisms through an intimate compatible interaction, thereby regulating complex biological and ecological mechanisms. In this context, we reviewed the current understanding of the biological phenomenon of allelopathy, which is mediated by phytotoxic compounds (called allelochemicals) released by plants into the soil that affect the growth, survival, development, ecological infestation, and intensification of other plant species and microbes in natural communities or agricultural systems. Advances in next-generation sequencing (NGS), such as metagenomics and metatranscriptomics, have opened the possibility of better understanding the effects of secreted metabolites on the composition and activity of root-associated microbial communities. Nevertheless, understanding the role of secretory metabolites in microbiome manipulation can assist in designing next-generation microbial inoculants for targeted disease mitigation and improved plant growth using the synthetic microbial communities (SynComs) tool. Besides a discussion on different approaches, we highlighted the advantages of conjugation of metabolomic approaches with genetic design (metabolite-based genome-wide association studies) in dissecting metabolome diversity and understanding the genetic components of metabolite accumulation. Recent advances in the field of metabolomics have expedited comprehensive and rapid profiling and discovery of novel bioactive compounds in root exudates. In this context, we discussed the expanding array of metabolomics platforms for metabolome profiling and their integration with multivariate data analysis, which is crucial to explore the biosynthesis pathway, as well as the regulation of associated pathways at the gene, transcript, and protein levels, and finally their role in determining and shaping the rhizomicrobiome.

A glimpse into the biosynthetic potential and resistome of microbial communities inhabiting sulfidic, chemoautotrophic Movile Cave ecosystem

Background: Microbial secondary metabolites (SM), especially those produced by soil microorganisms, have been a valuable source of antibiotics, antitumor agents, pigments, growth-promoting substances, etc., with tremendous market potential. These molecules are encoded by biosynthetic gene clusters (BGCs) within the bacterial genome. Their synthesis confers survival advantages by facilitating chemical defense, interspecies communication, and adaptation to well-defined ecological niches. Caves, particularly Movile Cave (Romania) - a sulfidic autotrophic-based ecosystem - can be considered extreme environments suited to investigate and discover novel bioactive microbial molecules. Here, low nutrient availability can lead to resource competition and, consequently, antimicrobial production to deter nearby microbial competitors. Aim: Our study focused on highlighting the biosynthetic gene clusters (BGCs) and biosynthetic potential of the sediment-associated microbiome in Movile Cave. Methods: Over 100 high-quality metagenome-assembled genomes (MAGs) were retrieved by whole-community shotgun-sequencing of 7 sediment samples collected in different Movile Cave’s galleries (Chiciudean et al. 2022). Detected MAGs were then analyzed for the presence of BGCs by antiSMASH (v. 6.1.1) (Blin et al. 2021) whereas antibiotic resistance genes were predicted by ResFinder (v. 4.1) (Florensa et al. 2022). The statistical analysis of BGCs data was performed by Past (v. 4.03). Results: We detected 637 BGCs across 106 high-quality MAGs that were affiliated to 22 phyla. The diversity of predicted BGCs varies across sediment samples with no apparent correlation to the number of analyzed MAGs per sample. The MAGs recovered from the sulfidic water-sediment interface (sample code PMV4) had the lowest alpha BGCs diversity among all sampled locations and it was clearly distinct in BGCs composition and abundance (β-diversity) from dry gallery samples (PMV7 and PMV8). The most abundant BGCs predicted in Movile Cave metagenomic dataset encode for terpenes, non-ribosomal peptides (NRPs) and ribosomally synthesised and post-translationally modified peptides (RIPPs). Acidobacteriota and Chloroflexota- affiliated MAGs were most enriched in BCG containing 20 and 23 BGCs per MAG, respectively, in contrast with the candidate phylum Ca. Patescibacteria-related MAGs that showed no SM biosynthetic capabilities. Two antimicrobial resistance (AR) genes (ole(C), oqxB) encoding resistance to antibiotics (i.e. oleandomycin, chloramphenicol, ciprofloxacin, trimethoprim) and disinfectants were identified in MAGs affiliated with the class Actinomycetia and Gammaproteobacteria. Based on the analyzed data, the biosynthetic potential of Movile Cave is significant compared with other microbiomes (Donia et al. 2014) and has a pronounced degree of novelty whereas the resistome (that is the genetic potential for antibiotic resistance) is reduced. Considering the uncommon futures of Movile Cave environment, future in-depth analysis of the identified BGCs might lead to the discovery of novel bioactive compounds. Additionally, the seclusion of this environment may provide an exciting opportunity for surveying the occurrence and environmental drivers of natural AR traits.

Epigenetic Modification: A Key Tool for Secondary Metabolite Production in Microorganisms.

Microorganisms are stupendous source of secondary metabolites, having significant pharmaceutical and industrial importance. Genome mining has led to the detection of several cryptic metabolic pathways in the natural producer of secondary metabolites (SMs) such as actinobacteria and fungi. Production of these bioactive compounds in considerable amount is, however, somewhat challenging. This led to the search of using epigenetics as a key mechanism to alter the expression of genes that encode the SMs toward higher production in microorganisms. Epigenetics is defined as any heritable change without involving the changes in the underlying DNA sequences. Epigenetic modifications include chromatin remodeling by histone posttranslational modifications, DNA methylation, and RNA interference. Biosynthetic gene cluster for SMs remains in heterochromatin state in which the transcription of constitutive gene is regulated by epigenetic modification. Therefore, small-molecule epigenetic modifiers, which promote changes in the structure of chromatin, could control the expression of silent genes and may be rationally employed for discovery of novel bioactive compounds. This review article focuses on the types of epigenetic modifications and their impact on gene expression for enhancement of SM production in microorganisms.

A Brief Review of Machine Learning-Based Bioactive Compound Research

Bioactive compounds are often used as initial substances for many therapeutic agents. In recent years, both theoretical and practical innovations in hardware-assisted and fast-evolving machine learning (ML) have made it possible to identify desired bioactive compounds in chemical spaces, such as those in natural products (NPs). This review introduces how machine learning approaches can be used for the identification and evaluation of bioactive compounds. It also provides an overview of recent research trends in machine learning-based prediction and the evaluation of bioactive compounds by listing real-world examples along with various input data. In addition, several ML-based approaches to identify specific bioactive compounds for cardiovascular and metabolic diseases are described. Overall, these approaches are important for the discovery of novel bioactive compounds and provide new insights into the machine learning basis for various traditional applications of bioactive compound-related research.

Identification of Antimicrobial Compounds in Two Streptomyces sp. Strains Isolated From Beehives.

The World Health Organization warns that the alarming increase in antibiotic resistant bacteria will lead to 2.7 million deaths annually due to the lack of effective antibiotic therapies. Clearly, there is an urgent need for short-term alternatives that help to alleviate these alarming figures. In this respect, the scientific community is exploring neglected ecological niches from which the prototypical antibiotic-producing bacteria Streptomycetes are expected to be present. Recent studies have reported that honeybees and their products carry Streptomyces species that possess strong antibacterial activity. In this study, we have investigated the antibiotic profile of two Streptomycetes strains that were isolated from beehives. One of the isolates is the strain Streptomyces albus AN1, which derives from pollen, and shows potent antimicrobial activity against Candida albicans. The other isolate is the strain Streptomyces griseoaurantiacus AD2, which was isolated from honey, and displays a broad range of antimicrobial activity against different Gram-positive bacteria, including pathogens such as Staphylococcus aureus and Enterococus faecalis. Cultures of S. griseoaurantiacus AD2 have the capacity to produce the antibacterial compounds undecylprodigiosin and manumycin, while those of S. albus AN1 accumulate antifungal compounds such as candicidins and antimycins. Furthermore, genome and dereplication analyses suggest that the number of putative bioactive metabolites produced by AD2 and AN1 is considerably high, including compounds with anti-microbial and anti-cancer properties. Our results postulate that beehives are a promising source for the discovery of novel bioactive compounds that might be of interest to the agri-food sector and healthcare pharmaceuticals.

Asymmetric construction of densely functionalized three-dimensional aza-tetracyclic scaffolds for drug discovery.

Asymmetric construction of densely functionalized three-dimensional aza-tetracyclic scaffolds were achieved by intramolecular Diels-Alder reaction of bicyclic precursors derived from L-tyrosine. Three substituents were systematically introduced into the developed scaffolds in various combinations, demonstrating their high utility in drug discovery.

A comprehensive review on chemistry and pharmacology of marine bioactives as antimetastatic agents

Metastasis by and large is responsible for the worldwide deaths associated with various types of cancers. The metastatic variant of cancer cells generated due to the cellular heterogeneity and abnormal activation of various signaling pathways in the tumor population leads to the progressive colonization of cancer cells in various organs. Over the years there has been a constant effort towards developing effective therapeutic strategies for the treatment and prevention of metastasis. The current conventional therapies have lacked efficacy due to the complex nature of metastasis involving multistep processes comprising tumor-tumor and tumor–extracellular matrix adhesion molecules, EMT, proteases, and tumor developing cell pathways. Albeit the exact mechanism of metastasis is somewhat still uncertain, there are a few recognized targets such as EMT markers, MMPs, serine proteases, microtubulin, angiogenic markers, and anoikis resistance, that have been identified as potential therapeutic targets for the inhibition of metastatic progression of cancer cells. Marine biodiversity offers unique chemical compounds due to the exposure to stressful environments for the discovery of novel bioactive compounds that are highly specific to these therapeutic targets. The review discusses various natural and semisynthetic compounds of marine origin having antimetastatic potential, focusing on the isolation, underlying mechanism of inhibition of multiple signaling pathways, and structural modification of isolated compounds for further development as drug candidates having superior clinical translation potential.

Medicinal plants of Aurora, Zamboanga del Sur, Philippines: Traditional knowledge and use amongst healers and locals

Health care quality and services can be significantly improved through the involvement of grassroots communities. In the Philippines, herbal medicines have been integrated into mainstream clinical practice to improve the healthcare system. However, knowledge of ethnopharmacology in the country is still limited, especially in rural areas like Aurora in Zamboanga del Sur— a municipality with a long history of herbal medicine usage. This study aims to document folk healing practices, utilization, and knowledge of medicinal plants and to quantitatively evaluate ethnopharmacological data from the area. This study documented 165 ethnomedicinal plant species from 64 families, categorized into 16 use categories. We found differences in medicinal plant knowledge based on age, social status, and occupation but not gender. Ethnopharmacological utilization of plants among informants was in strong agreement, with the highest number of species (71) used to treat digestive problems. Several interesting features of local folk medicine were noted, including tuga (healing power bestowed by gods and spirits) and himulso (pulse analysis). Concepts of people–plant interactions and the doctrine of signatures were also observed. Several plant species identified in this study remain understudied; thus, our documentation provides a starting point for the discovery of novel bioactive compounds while promoting pharmacovigilance. This study will also serve as a reference for establishing better management and conservation strategies of floral resources and culture in the area.

Fungal Endophytes: A Promising Frontier for Discovery of Novel Bioactive Compounds.

For years, fungi have served as repositories of bioactive secondary metabolites that form the backbone of many existing drugs. With the global rise in infections associated with antimicrobial resistance, in addition to the growing burden of non-communicable disease, such as cancer, diabetes and cardiovascular ailments, the demand for new drugs that can provide an improved therapeutic outcome has become the utmost priority. The exploration of microbes from understudied and specialized niches is one of the promising ways of discovering promising lead molecules for drug discovery. In recent years, a special class of plant-associated fungi, namely, fungal endophytes, have emerged as an important source of bioactive compounds with unique chemistry and interesting biological activities. The present review focuses on endophytic fungi and their classification, rationale for selection and prioritization of host plants for fungal isolation and examples of strategies that have been adopted to induce the activation of cryptic biosynthetic gene clusters to enhance the biosynthetic potential of fungal endophytes.

Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer's Disease.

Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.

Recent advances in the discovery of novel marine natural products and mycosporine-like amino acid UV-absorbing compounds.

Bioactive compounds from marine environments represent a rich source of bioproducts for potential use in medicine and biotechnology. To discover and identify novel marine natural products (MNPs), evaluating diverse biological activities is critical. Increased sensitivity and specificity of omics technologies, especially next-generation high-throughput sequencing combined with liquid chromatography-mass spectrometry and nuclear magnetic resonance, are speeding up the discovery of novel bioactive compounds. Mycosporine-like amino acids (MAAs) isolated from many marine microorganisms are among highly promising MNPs characterized by ultraviolet radiation (UV) absorbing capacities and are recognized as a potential source of ecologically friendly sunscreens. MAAs absorb damaging UV radiation with maximum absorption in the range of 310–360 nm, including both UVA and UVB ranges. MAAs are also characterized by other biological activities such as anti-oxidant, anti-cancer, and anti-inflammatory activities. The application of modern omics approaches promoted some recent developments in our understanding of MAAs’ functional significance and diversity. This review will summarize the various modern tools that could be applied during the identification and characterization of MNPs, including MAAs, to further their innovative applications.Key points • New omics technologies are speeding up the discovery of novel bio-products • The vast diversity of bioactive capacities of marine natural products described • Marine microorganisms as a source of environmentally friendly sunscreens