Beneficial Secondary Metabolites Research Articles

A critical review on the active anti-viral metabolites of bioprospecting traditionally used plant species from semi-arid regions of the subcontinent.

Plants are crucial medicinal resources, with 80 % of people relying on them for primary healthcare. The search for natural antiviral compounds is increasing, especially in semi-arid ecosystems where abiotic stress promotes the production of beneficial secondary metabolites. This review highlights semi-arid plants with the potential as functional foods to combat viral diseases and other illnesses. Literature was searched in databases like ScienceDirect to gather information on novel compounds from stress-tolerant semi-arid plant species. These compounds have potential uses in treating viral infections and other health issues such as diabetes and high blood pressure. The review screened 61 semi-arid plants known for their antiviral metabolites. Eight plants were identified with novel antiviral compounds. Key metabolites include agathisflavone, pectic arabinogalactan, azadirachtin, aloin, aloe-emodin, aloesaponarin I, allicin, terpenoids, chlorogenic acids, curcumin, chromones, β-sitosterol, lupeol, oleuropein, carissol, β-amyrin, and ∆-9-tetrahydrocannabinol. Stress-tolerant semi-arid plants are significant sources of metabolites for treating infectious diseases and boosting immune systems. Further research on these metabolites in animal models is needed to verify their efficacy for treating human diseases during endemic and pandemic outbreaks, such as COVID-19.

MpDLDH gene is crucial for regulating growth and pigment biosynthesis through acetyl-CoA modulation in Monascus purpureus

Monascus spp. are traditional medicinal and edible filamentous fungi in Asian countries. Monascus pigments (MPs) are the most well-known beneficial secondary metabolites produced by Monascus and used as natural food colorants with a long history. However, the understanding of the MPs biosynthesis remains limited due to their complexity and diversity, and the known MPs biosynthetic gene cluster (BGC) is also incomplete. In this study, we re-predicted the MPs BGC based on the genome sequence of Monascus purpureus and found seven new genes that may be involved in MPs biosynthesis. Among them, MpDLDH encodes a putative dihydrolipoamide dehydrogenase, which is the E3 subunit of pyruvate dehydrogenase (PDH) multiunit complex for catalyzing pyruvate to acetyl-CoA. MpDLDH knockout significantly decreased the acetyl-CoA content, and resulted in small pale colony, dramatically reduced biomass, few conidia, and absence of cleistothecia. MpDLDH deletion seriously repressed MPs biosynthesis, but did not change its composition. In addition to the increase of intracellular MPs production and acetyl-CoA in the late growth stage on solid medium, MpDLDH overexpression had no obvious effect on the phenotypes. Since acetyl-CoA is the crucial substrate for both MPs biosynthesis and tricarboxylic acid cycle, it is believed that MpDLDH of MPs BGC plays a key role in regulating cell growth, development and pigment formation through participating in the assembly of PDH complex to modulate the production of acetyl-CoA. These findings may deepen our understanding of the regulatory mechanisms between MPs biosynthesis and cell growth in Monascus species.

Natural volatile organic compounds (NVOCs) and airborne microorganisms in different stands of urban forests

Natural volatile organic compounds (NVOCs) and airborne microorganisms are important elements in urban forest air that affect air quality and human health. In this study, the Zhuyu Bay urban forest in Yangzhou was selected as the research object, and gas chromatography–mass spectrometry (GC–MS) was used to detect the composition of NVOCs in different forest stands. Terpenes, heterocyclic compounds, and esters accounted for the highest proportions. We then explored the effects of NVOCs on the physiological health of each forest stand and used Kyoto Encyclopedia of Genes and Genome enrichment analysis to identify beneficial secondary metabolites. Among the identified compounds, alpha-phellandrene 1, azulene, and other terpenoids were found to possess antibacterial, anti-inflammatory, and antioxidant properties. Heterocyclic compounds, such as 4-Pyridinecarboxylic acid and visnagin, showed significant effects in the treatment of diseases. In addition, we collected and analyzed culturable airborne microorganisms in different forest stands and found that the bamboo forest had the lowest number of culturable airborne microorganisms. To further explore the influence of urban microclimates on air microorganisms and NVOCs, a partial least squares path modelling (PLS-PM) analysis was conducted. Air negative oxygen ion is an important factor affecting NVOCs, and Air moisture has a significant positive effect on bacteria proportion.

The potential of bacterial endophytes on orchids

Orchids are one of the most exquisite and diverse plant species in nature. The seeds of orchids are non-endospermic and, therefore, dependent on endophytes for germination, growth, and adaptability. Orchids are prized for their beauty and therapeutic and culinary qualities by naturalists and the general public. Many orchid species are now endangered or vulnerable due to collectors' eagerness to take them. Current studies on orchids have concentrated on isolating and identifying the mycorrhizal and non-mycorrhizal endophytes that either directly or indirectly help orchids to grow, develop, and produce beneficial secondary metabolites. In orchids, bacterial endophytes play an essential role in the formation of mycorrhizae and the stability of relationships between plants and fungi. Endophytic bacteria can grow in orchids by producing phytohormones, doing photosynthesis, fixing nitrogen, promoting the mineral nutrition cycle, forming siderophores, and producing diverse beneficial metabolites to improve biomass production, stress tolerance, and biocontrol of potential phytopathogenic fungal species. This article examines how endophytic bacteria are associated with orchids and their potential growth-promoting abilities.

Variations in photoperiods and their impact on yield, photosynthesis and secondary metabolite production in basil microgreens

BackgroundThe effects of different photoperiods on plant phytochemical synthesis can be improved by adjusting the daily light integral. Photoperiod is one of the most important environmental factors that control growth, plant’s internal rhythm and the synthesis of secondary metabolites. Information about the appropriate standard in terms of photoperiod for growing basil microgreens as one of the most important medicinal plants is limited. In this study, the effects of five different photoperiods, 6 (6 h × 3 cycles), 8 (8 h × 2 cycles), 16, 18, and 24 h day− 1 on the yield, photosynthesis and synthesis of secondary metabolites of three cultivars and one genotype of basil microgreens in floating system were evaluated. The purpose of this research was to determine the feasibility of using permanent light in growing basil microgreens and to create the best balance between beneficial secondary metabolites and performance.ResultsThe results showed that the effects of photoperiod and cultivar on all investigated traits and their interaction on photosynthetic pigments, antioxidant capacity, total phenolic compounds, proline content and net photosynthesis rate were significantly different at the 1% level. The highest levels of vitamin C, flavonoids, anthocyanins, yield and antioxidant potential composite index (APCI) were obtained under the 24-h photoperiod. The highest antioxidant capacity was obtained for the Kapoor cultivar, and the highest total phenolic compound and proline contents were measured for the Ablagh genotype under a 24-h photoperiod. The highest yield (4.36 kg m− 2) and APCI (70.44) were obtained for the Ablagh genotype. The highest nitrate content was obtained with a photoperiod of 18 h for the Kapoor cultivar. The highest net photosynthesis rate was related to the Violeto cultivar under a 24-hour photoperiod (7.89 μmol CO2 m− 2 s− 1). Antioxidant capacity and flavonoids had a positive correlation with phenolic compounds and vitamin C. Yield had a positive correlation with antioxidant capacity, flavonoids, vitamin C, APCI, and proline.ConclusionsUnder continuous light conditions, basil microgreens resistance to light stress by increasing the synthesis of secondary metabolites and the increase of these biochemical compounds made basil microgreens increase their performance along with the increase of these health-promoting compounds. The best balance between antioxidant compounds and performance was achieved in continuous red + blue light. Based on these results, the use of continuous artificial LED lighting, due to the increase in plant biochemical with antioxidant properties and yield, can be a suitable strategy for growing basil microgreens in floating systems.

Влияние фитохимического и антиоксидантного составов необработанных водных экстрактов Chlorella vulgaris на рост Saccharomyces cerevisiae в спиртовой среде

Chlorella vulgaris is rich in secondary metabolites that defend against environmental stress and aid in detoxification. In particular, bioactive compounds extracted from C. vulgaris may enhance the growth of microorganisms and detoxify them in an ethanolic medium. We aimed to effectively extract and characterize bioactive compounds found in C. vulgaris and further test them for their beneficial effects on the growth of Saccharomyces cerevisiae cultured in an ethanolic medium. Bioactive compounds in C. vulgaris were extracted using ultrasound and water as solvents. The extracts were analyzed for total phenol and flavonoid contents as part of their phytochemical composition. Their DPPH radical activity and Hydrogen peroxide scavenging activity were examined to determine their antioxidant properties and protective potential for S. cerevisiae in an ethanolic medium. Further, the extracts were added at 0.1, 0.5, 1, 2, 3, and 4% w/v concentrations into S. cerevisiae culture induced with 1% v/v ethanol for 23 days. The yeast cells’ density and viability were measured after 2, 5, 9, 13, 17, and 23 days. The extracts of C. vulgaris were rich in phenols and flavonoids, which are important bioactive compounds. Higher concentrations of the extracts increased total phenols up to 47.67 GAE mg/L and total flavonoids up to 218.67 QE mg/L. The extracts’ antioxidant composition showed high DPPH activity (70.12%) and H2O2 scavenging activity (4.97%). After 23 days, the samples treated with C. vulgaris extracts maintained a high viability of the yeast cells. In particular, the samples with 2, 4, 0.1, and 1% of the extract had a cell viability of 95.75, 94.04, 89.15, and 74%, respectively. The positive control (1% ethanol alone) and negative control (yeast alone) had 47.71 and 21.01% viability, respectively. This drastic reduction in viability was due to lysis of the yeast cells caused by ethanol. Ultrasound extraction with water as a solvent produced abundant beneficial secondary metabolites from C. vulgaris. The addition of C. vulgaris extract increased the viability and cell density of S. cerevisiae after 27 days, thereby protecting the yeast cells from the toxic effects of ethanol.

Comparative transcriptome database for Camellia sinensis reveals genes related to the cold sensitivity and albino mechanism of 'Anji Baicha'.

Tea, a globally popular beverage, contains various beneficial secondary metabolites. Tea plants (Camellia sinensis) exhibit diverse genetic traits across cultivars, impacting yield, adaptability, morphology, and secondary metabolite composition. Many tea cultivars have been the subject of much research interest, which have led to the accumulation of publicly available RNA-seq data. As such, it has become possible to systematically summarize the characteristics of different cultivars at the transcriptomic level, identify functional genes, and infer gene functions through co-expression analysis. Here, the transcriptomes of 9 tea cultivars were assembled, and comparative analysis was conducted on the coding sequences of 13 cultivars. To give access to this data, we present TeaNekT (https://teanekt.sbs.ntu.edu.sg/), a web resource that facilitates the prediction of gene functions of various tea cultivars. We used TeaNekT to perform a cross-cultivar comparison of co-expressed gene clusters and tissue-specific gene expression. We observed that 'Anji Baicha' possesses the highest number of cultivar-specific genes and the second-highest number of expanded genes. These genes in 'Anji Baicha' tend to be enriched in functions associated with cold stress response, chloroplast thylakoid structure, and nitrogen metabolism. Notably, we identified three significantly expanded homologous genes in 'Anji Baicha' encoding the ICE1, SIZ1, and MAPKK2, which are closely associated with the cold sensitivity of 'Anji Baicha'. Additionally, one significantly expanded homologous gene in 'Anji Baicha' encoding regulatory factor RIQ may play a crucial role in the abnormal chloroplast structure and absence of thylakoid membranes in 'Anji Baicha'.

Luminescent Quantum Dot Films Increase the Radiation Capture and Yield of Lettuce and Sweet Basil Compared to a Traditional/Neutral-density Greenhouse Glazing

Utilizing quantum dot (QD) luminescent films as a greenhouse covering material is an innovative method of modifying the greenhouse light spectrum. The QD films convert a portion of high-energy ultraviolet and blue photons to lower-energy photons. Previous research has shown that the application of QD films in greenhouses led to improved crop yields of red lettuce and tomatoes. However, the underlying mechanism of the yield increases has not been fully explored. We quantified the effects of solar spectral shifts attributable to QD films on plant morphology, radiation capture, and, subsequently, crop yield. Green and red leaf lettuces and basil were grown in a greenhouse under four treatments: regular-concentration QD film (reg QD film); high-concentration QD film (high QD film); color-neutral polyethylene (PE) film; and control treatment without any films. Compared to the reg QD film, the high QD film converted a higher fraction of blue photons into longer-wavelength photons, resulting in enhanced leaf expansion, stem elongation, and shoot fresh weight of red lettuce and basil compared with those grown under the PE film without spectral modifications. No significant growth differences were observed between the control and high QD film treatments of red lettuce and basil despite a 23% reduction in the average daily light integral (DLI) under the high QD film treatment. Compared to that grown under the control treatment, green lettuce grown under the high QD film treatment had a similar total leaf area but reduced shoot biomass; this was likely associated with reductions in leaf thickness and chlorophyll content. In contrast, the red lettuce showed more pronounced leaf expansion and reduced leaf anthocyanin content under the high QD film, which likely helped to offset the reduction in DLI. Overall, our results indicated that modifying the solar spectrum with QD films as greenhouse covering material could result in improved crop radiation capture and yield in greenhouse production of lettuce and basil. However, the spectral shifts caused by the QD films may affect crop quality attributes, such as anthocyanin levels and the production of other beneficial secondary metabolites. This effect on crop quality should be carefully considered and requires further study.

Papaya extract as a prebiotic strengthens the inhibitory activity of lactobacillus against the growth of pathogenic bacteria

Abstract The flesh leaves, and seeds of papaya contain carbohydrates and dietary fiber that were suggested capable of being metabolized by intestinal microbiota such as L. casei and L. plantarum to produce beneficial secondary metabolites for body health. The effect of papaya flesh, leaf, and seed extracts on L. plantarum and L. casei growth and the synbiotic effect of papaya flesh extract with L. plantarum on the growing of S. aureus, E. coli, and P. aeruginosa in this study, was investigated. Diffusion of paper discs impregnated with various concentrations of the extract was utilized to determine the bacterial growth zone of L. casei, and solid media to calculate the total bacterial population in co-feeding L. plantarum and P. aeruginosa or with S. aureus and E. coli in the presence of papaya flesh extract to determine its synbiotic effect. All extracts increase the growth of L. casei and L. plantarum bacteria. Synbiotic papaya flesh extract suppresses the bacterial growth of P. aeruginosa, S. aureus, and E. coli in a concentration-dependent manner. It is concluded that papaya is a promising prebiotic source, to strengthen the effect of L. plantarum to inhibit the growth of pathogenic bacteria.

Enhancing the Nutritional Profile of Crataegus monogyna Fruits by Optimizing the Extraction Conditions

Crataegus monogyna (CM) fruits are highly regarded for their rich nutritional content, boasting elevated levels of various beneficial secondary metabolites like total polyphenols, including anthocyanins, and ample amounts of ascorbic acid and antioxidant activity. Despite the acknowledged benefits of CM fruits, researchers have directed more attention toward its leaves and flowers. Consequently, the current research attempts to optimize extraction techniques for CM fruit using a multifaceted approach involving varied durations, temperatures, and concentrations of ethanol solvent to isolate the diverse range of bioactive components present effectively. High-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) is employed for the identification and quantification of polyphenolic compounds. According to the results, by following the optimum extraction parameters (50% ethanolic solvent, 50 °C extraction temperature, and 60 min extraction time), the total polyphenol content can be increased up to 410%, reaching 55.59 mg gallic acid equivalents/g. Using 50% ethanolic solvent, 80 °C extraction temperature, and extraction time of 90 min, the total anthocyanin content can be enhanced by more than 560%, reaching a quantity of 51.83 μg cyanidin equivalents/g. Moreover, the antioxidant activity of CM fruit extracts can reach 415.95 μmol ascorbic acid equivalents (AAE)/g dw (by FRAP method), using 50% ethanolic solvent, 50 °C extraction temperature, and 60 min extraction time, and 270.26 μmol AAE/g dw (by DPPH method) and 1053.28 mg/100 g dw ascorbic acid content, using 50% ethanolic solvent, 80 °C extraction temperature, and 90 min extraction time. This comprehensive study seeks to augment the already substantial content of bioactive compounds found in CM, resulting in an extract with promising applications across the pharmaceutical, food, and cosmetics industries.

N-Acetylglutamic Acid Enhances Tolerance to Oxidative and Heat Stress in Humulus lupulus

Humulus lupulus (hop) is a necessary material in beer brewing because its female inflorescences (called hop cones) give a floral aroma, bitterness and foam stability to beer. Various aspects of growth conditions in the cultivation area, especially temperature, strongly affect the yield and quality of hop cones. Recent estimates suggest that climate change accompanied by global warming is negatively impacting hop production, with high temperatures reducing the expression of genes that regulate beneficial secondary metabolites in hops. This underscores the need for techniques to enhance hop tolerance to high temperatures. This study explores the potential of N-acectylglutamic acid (NAG), a non-proteinogenic amino acid, to confer hops with tolerance against oxidative and heat stress by suppressing ROS accumulation. Exogenous NAG treatment activated the expression of HlZAT10/12 and HlHSFA2, which are putative homologues considered master regulators in response to oxidative and heat stress in Arabidopsis thaliana (Arabidopsis). Additionally, histone acetylation, a histone modification associated with transcriptional activation, was increased at these stress-responsive genes in the NAG-treated hops. These findings reveal NAG as a potential chemical compound to mitigate hop production reduction caused by high temperatures and suggest the conservation of epigenetic modification-mediated regulation of gene expression in response to environmental stresses in hops.

A method for mining condition-specific co-expressed genes in Camellia sinensis based on k-means clustering

BackgroundAs one of the world’s most important beverage crops, tea plants (Camellia sinensis) are renowned for their unique flavors and numerous beneficial secondary metabolites, attracting researchers to investigate the formation of tea quality. With the increasing availability of transcriptome data on tea plants in public databases, conducting large-scale co-expression analyses has become feasible to meet the demand for functional characterization of tea plant genes. However, as the multidimensional noise increases, larger-scale co-expression analyses are not always effective. Analyzing a subset of samples generated by effectively downsampling and reorganizing the global sample set often leads to more accurate results in co-expression analysis. Meanwhile, global-based co-expression analyses are more likely to overlook condition-specific gene interactions, which may be more important and worthy of exploration and research.ResultsHere, we employed the k-means clustering method to organize and classify the global samples of tea plants, resulting in clustered samples. Metadata annotations were then performed on these clustered samples to determine the “conditions” represented by each cluster. Subsequently, we conducted gene co-expression network analysis (WGCNA) separately on the global samples and the clustered samples, resulting in global modules and cluster-specific modules. Comparative analyses of global modules and cluster-specific modules have demonstrated that cluster-specific modules exhibit higher accuracy in co-expression analysis. To measure the degree of condition specificity of genes within condition-specific clusters, we introduced the correlation difference value (CDV). By incorporating the CDV into co-expression analyses, we can assess the condition specificity of genes. This approach proved instrumental in identifying a series of high CDV transcription factor encoding genes upregulated during sustained cold treatment in Camellia sinensis leaves and buds, and pinpointing a pair of genes that participate in the antioxidant defense system of tea plants under sustained cold stress.ConclusionsTo summarize, downsampling and reorganizing the sample set improved the accuracy of co-expression analysis. Cluster-specific modules were more accurate in capturing condition-specific gene interactions. The introduction of CDV allowed for the assessment of condition specificity in gene co-expression analyses. Using this approach, we identified a series of high CDV transcription factor encoding genes related to sustained cold stress in Camellia sinensis. This study highlights the importance of considering condition specificity in co-expression analysis and provides insights into the regulation of the cold stress in Camellia sinensis.

Genetic characterization and evaluation of pigmented maize (Zea mays L.) landraces of the North East Hill Region of India-an established centre of maize diversity

Abstract The North East Hill Region (NEHR) of India is home to diverse maize landraces including pigmented accessions rich in antioxidants and nutritional properties. The present study attempted to characterize a representative collection of this mostly unexplored diversity. Altogether eighty-three local maize landraces from the seven hill states of the NEHR were studied with special emphasis on pigmentation diversity. For the morphological traits, a significant ANOVA indicated the presence of substantial genetic variability for which selection would be fruitful. A number of these accessions were found to have traits that help cope with moisture stress, improve stalk strength and optimize photosynthesis. Principal component analysis studies for the yield attributing traits indicated that ear weight was most variable. The bleaching/histological studies confirmed that anthocyanin pigment when present was always restricted to the aleurone layer of the kernels, typical of blue maize. Quantitative analysis for kernel anthocyanin/phlobaphene content also revealed genetic differences among the accessions. Genetic analysis using the model-based STRUCTURE indicated significant population structuring among the accessions. Specifically, for the pigmentation diversity studies both principal coordinate analysis and neighbour joining methods revealed near concurrent population structuring due in part to the high differentiation of seven of the twenty-one pigmentation specific loci studied. The results obtained provide comprehensive evidence of a significant amount of genetic differentiation among the landraces under study. Landraces are valuable reservoirs of favourable alleles for which selection can be made and, as in this study, identify accessions for breeding maize with enhanced levels of beneficial secondary metabolites.

Pseudostellaria heterophylla improves intestinal microecology through modulating gut microbiota and metabolites in mice.

Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

Monascus spp. are commercially important fungi due to their ability to produce beneficial secondary metabolites such as the cholesterol-lowering agent lovastatin and natural food colorants azaphilone pigments. Although hyphal branching intensively influenced the production of these secondary metabolites, the pivotal regulators of hyphal development in Monascus spp. remain unclear. To identify these important regulators, we developed an artificial intelligence (AI)–assisted image analysis tool for quantification of hyphae-branching and constructed a random T-DNA insertion library. High-throughput screening revealed that a STE kinase, MpSTE1, was considered as a key regulator of hyphal branching based on the hyphal phenotype. To further validate the role of MpSTE1, we generated an mpSTE1 gene knockout mutant, a complemented mutant, and an overexpression mutant (OE::mpSTE1). Microscopic observations revealed that overexpression of mpSTE1 led to a 63% increase in branch number while deletion of mpSTE1 reduced the hyphal branching by 68% compared to the wild-type strain. In flask cultures, the strain OE::mpSTE1 showed accelerated growth and glucose consumption. More importantly, the strain OE::mpSTE1 produced 9.2 mg/L lovastatin and 17.0 mg/L azaphilone pigments, respectively, 47.0% and 30.1% higher than those of the wild-type strain. Phosphoproteomic analysis revealed that MpSTE1 directly phosphorylated 7 downstream signal proteins involved in cell division, cytoskeletal organization, and signal transduction. To our best knowledge, MpSTE1 is reported as the first characterized regulator for tightly regulating the hyphal branching in Monascus spp. These findings significantly expanded current understanding of the signaling pathway governing the hyphal branching and development in Monascus spp. Furthermore, MpSTE1 and its analogs were demonstrated as promising targets for improving production of valuable secondary metabolites.Key points• MpSTE1 is the first characterized regulator for tightly regulating hyphal branching• Overexpression of mpSTE1 significantly improves secondary metabolite production• A high-throughput image analysis tool was developed for counting hyphal branching

Significant enhancement of edible Monascus azaphilone pigments production via targeted improvement of the expression of histone deacetylase MrHos2

Monascus azaphilone pigments (MonAzPs) are beneficial secondary metabolites secreted by Monascus spp., which have great potentials to be used in industrial fields besides food industry. But there is very little knowledge about their regulatory mechanism, which limits the large-scale production and utilization of MonAzPs. In this study, we firstly studied the effect on MonAzPs production by inhibiting and enhancing histone deacetylase gene hos2 (Mrhos2) expression in Monascus ruber. UPLC detection revealed that inactivation of Mrhos2 dramatically decreased MonAzPs production, while overexpression of Mrhos2 significantly increased MonAzPs production. Transcriptional level analysis shows Mrhos2 regulates expression of MonAzPs biosynthesis genes. Immunoaffinity enrichment assisted mass spectrometry assay reveals deletion of Mrhos2 perturbs lysine acetylation of enzymes in the metabolic pathway of acetyl-CoA and malonyl-CoA. Collectively, transcription activation and protein acetylation modification mediated by MrHos2 are involved in regulating the MonAzPs production, and MrHos2 can be used as a target to increase MonAzPs production.

Alzheimer's Disease-Related Proteins Targeted by Secondary Metabolite Compounds from Streptomyces: A Scoping Review.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized as rapid and progressive cognitive decline affecting 26 million people worldwide. Although immunotherapies are ideal, its clinical safety and effectiveness are controversial, hence, treatments are still reliant on symptomatic medications. Concurrently, the Streptomyces genus has attracted attention given its pharmaceutically beneficial secondary metabolites to treat neurodegenerative diseases. To present secondary metabolites from Streptomyces sp. with regulatory effects on proteins and identified prospective target proteins for AD treatment. Research articles published between 2010 and 2021 were collected from five databases and 83 relevant research articles were identified. Post-screening, only 12 research articles on AD-related proteins were selected for further review. Bioinformatics analyses were performed through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) network, PANTHER Go-Slim classification system (PANTHER17.0), and Kyoto Encyclopedia of Genes and Genomes (KEGG) Mapper. A total of 20 target proteins were identified from the 12 shortlisted articles. Amyloid-β, BACE1, Nrf-2, Beclin-1, and ATG5 were identified as the potential target proteins, given their role in initiating AD, mitigating neuroinflammation, and autophagy. Besides, 10 compounds from Streptomyces sp., including rapamycin, alborixin, enterocin, bonnevillamides D and E, caniferolide A, anhydroexfoliamycin, rhizolutin, streptocyclinone A and B, were identified to exhibit considerable regulatory effects on these target proteins. The review highlights several prospective target proteins that can be regulated through treatments with Streptomyces sp. compounds to prevent AD's early stages and progression. Further identification of Streptomyces sp. compounds with potential anti-AD properties is recommended.

6-Pentyl-α-Pyrone from Trichoderma gamsii Exert Antioxidant and Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Mouse Macrophages.

Filamentous fungi produce several beneficial secondary metabolites, including bioactive compounds, food additives, and biofuels. Trichoderma, which is a teleomorphic Hypocrea that falls under the taxonomic groups Ascomycota and Dikarya, is an extensively studied fungal genus. In an ongoing study that seeks to discover bioactive natural products, we investigated potential bioactive metabolites from the methanolic extract of cultured Trichoderma gamsii. Using liquid chromatography-mass spectrometry (LC-MS), one major compound was isolated and structurally identified as 6-pentyl-α-pyrone (6PP) based on nuclear magnetic resonance data and LC-MS analysis. To determine its antioxidant and anti-inflammatory activity, as well as the underlying mechanisms, we treated lipopolysaccharide (LPS)-stimulated Raw264.7 mouse macrophages with 6PP. We found that 6PP suppresses LPS-induced increase in the levels of nitric oxide, a mediator of oxidative stress and inflammation, and restores LPS-mediated depletion of total glutathione by stabilizing nuclear factor erythroid 2-related factor 2 (Nrf2), an antioxidative factor, and elevating heme oxygenase-1 levels. Furthermore, 6PP inhibited LPS-induced production of proinflammatory cytokines, which are, at least in part, regulated by heme oxygenase-1 (HO-1). 6PP suppressed proinflammatory responses by inhibiting the nuclear localization of nuclear factor kappa B (NF-κB), as well as by dephosphorylating the mitogen-activated protein kinases (MAPKs). These results indicate that 6PP can protect macrophages against oxidative stress and LPS-induced excessive inflammatory responses by activating the Nrf2/HO-1 pathway while inhibiting the proinflammatory, NF-κB, and MAPK pathways.

Camellia sinensis L. Extract Suppresses Inflammation on Acute Respiratory Distress Syndrome Cells Models via Decreasing IL-1ß, IL-6 and COX-2 Expressions

Acute Respiratory Distress Syndrome (ARDS) is one of the clinical manifestations in severe COVID-19 patients characterized by acute inflammation resulting in respiratory failure and death. Camellia sinensis L. or green tea extract has many beneficial secondary metabolites including polyphenols which have anti-inflammatory and anti-viral roles. This study was aimed to investigate the activity of green tea extract (GTE) as an anti-inflammatory on ARDS model cells. In this study, rat lung alveolar type II epithelial cells line (L2) was induced by lipopolysaccharide (LPS) to mimic the inflammation process in ARDS. These cells were then treated with GTE to determine the GTE effectiveness in reducing the inflammation. The GTE polyphenol constitutions were first confirmed using Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS). The cytotoxic assay was conducted using MTS assay kit to determine the safe range of GTE concentrations that used in the next assay. The effectiveness of the GTE was determined by measuring pro-inflammatory cytokines (IL-1ß and IL-6) and inflammation-mediated enzymes (COX-2), both of which were by ELISA method. Furthermore, this study measured the ACE-2 and TMPRSS-2 gene expressions by qRT-PCR method. The results showed that GTE treatment significantly reduced pro-inflammatory cytokines IL-1ß, IL-6, inflammation-mediated enzyme COX-2, and significantly increased ACE-2 and TMPRSS-2 mRNA expressions. In short, green tea extract possesses the potential to alleviate inflammation. HIGHLIGHTS Acute Respiratory Distress Syndrome (ARDS) is one of clinical manifestations in severe COVID-19 patients characterized by acute inflammation results in respiratory failure and death In lung inflammation, the Angiotensin Converting Enzyme-2 (ACE-2) and Trans-Membrane Protease Serine-2 (TMPRSS-2) genes were lowly expressed, then causes alveolar tissue collapse High levels of inflammatory mediator cytokines would be secreted in respiratory tracts, such as Interleukin (IL)-1β, IL-6, and Cyclooxygenases (COX)-2 Polyphenols in green tea (Camelia sinensis L.) have been reported to have anti-inflammatory activities GRAPHICAL ABSTRACT

Isolation and Identification of Endophytic Bacterial Isolates from the Leaves, Roots, and Stems Parts of Artemisia annua, Moringa oleifera, and Ocimum lamiifolium Plants.

Medicinal plants are known to harbor diverse species of endophytic bacteria which are known for secretion of beneficial secondary metabolites, like enzymes and antimicrobial compounds. The present study aimed to isolate, characterize, and identify the endophytic bacteria isolates from Artemisia annua, Moringa oleifera, and Ocimum lamiifolium plants. Certain endophytic bacterial isolates were screened. Phosphate and Zinc solubilization were performed for newly obtained isolates. The 16S rRNA gene sequencing was performed for RPAAI-8 isolate. Data were analyzed. Our study showed that endophytic bacterial isolates were recognized to be Bacillus cereus, B. subtilis, Citrobacter freundii, Enterobacter asburiae, E. cloacae, E. kobei, E. ludwigii, Enterococcus faecium, and Pseudomonas monteilli. From among these differentiated endophytic bacterial isolates, Enterobacter species are the most frequently obtained isolates. These bacterial isolates were shown 99.77% sequence similarity to Enterobacter ludwigii EN-119T (JTLO01000001) using 16S rRNA gene sequencing. This isolate was designated as Enterobacter sp. RPAAI-8. This isolate was able to employ selected cheap and cost-effective agro wastes as a carbon source. This cheap agro waste utilization by these Enterobacter species could be the first report. In conclusion, the present isolates are found to be employed for plant growth promotion and solubilizing insoluble phosphate and zinc. Before this time, most of the recent isolates were not identified from these medicinal plants. The ethyl acetate extract of the isolates also showed inhibitory activity against selected test pathogens.