Variety Of Secondary Metabolites Research Articles

Whole genome analysis, detoxification of ochratoxin a and physiological characterization of a novel Bacillus velezensis MM35 isolated from soil

Ochratoxin A (OTA) is a significant global contaminant that poses severe challenges to food safety and public health. This study aims to isolate the OTA-degrated probiotics and evaluate genetic and biological characteristic. Here, The degradation rate of a new strain named Bacillus velezensis MM35 isolated from soil was the highest (87.10% within 48 h), and its culture supernatant was the main component of OTA degradation (63.95%) by high performance liquid chromatography. Further investigation revealed that the extracellular enzyme that degrades OTA in the culture supernatant of MM35 may be a small molecule enzyme with certain heat resistance. Genome-wide analysis showed that MM35 contains a cluster of carboxypeptidases encoding OTA-degrading potential, and had good metabolic and catalytic synthesis ability, and strong application potential in the synthesis and degradation of carbohydrates and proteins. A variety of secondary metabolites with antibacterial properties, such as non-ribosomal peptide synthetase and terpenoids, were identified in its metabolites. Consistent with the predicted results, MM35 showed various enzyme production characteristics such as cellulase and xylanase. Furthermore, MM35 could inhibit the growth of a variety of pathogenic bacteria, and showed high co-aggregation ability to Escherichia coli and Salmonella typhimurium. In addition, MM35 has certain tolerance to harsh environments such as strong acid, bile salt, and high temperature. Additionally, the adhesion rate of MM35 was 5.4%, and the invasion rate was 2.1% in IPEC-J2 cells. In summary, the data suggest MM35 isolated strain has high OTA degradation efficiency, antibacterial activity and intestinal colonization, which provided a new way for the treatment of OTA contamination in food and feed industries.

Bis-Iridoid Glycosides and Triterpenoids from Kolkwitzia amabilis and Their Potential as Inhibitors of ACC1 and ACL

A comprehensive phytochemical investigation of the twigs/leaves and flower buds of Kolkwitzia amabilis, a rare deciduous shrub native to China, led to the isolation of 39 structurally diverse compounds. These compounds include 11 iridoid glycosides (1–4 and 7–13), 20 triterpenoids (5, 6, and 14–31), and 8 phenylpropanoids (32–39). Among these, amabiliosides A (1) and B (2) represent previously undescribed bis-iridoid glycosides, while amabiliosides C (3) and D (4) feature a unique bis-iridoid-monoterpenoid indole alkaloid scaffold with a tetrahydro-β-carboline-5-carboxylic acid moiety. Amabiliacids A (5) and B (6) are 24-nor-ursane-type triterpenoids characterized by an uncommon ∆11,13(18) transannular double bond. Their chemical structures and absolute configurations were elucidated through spectroscopic data and electronic circular dichroism analyses. Compound 2 exhibited a moderate inhibitory effect against acetyl CoA carboxylase 1 (ACC1), with an IC50 value of 9.6 μM. Lonicejaposide C (8), 3β-O-trans-caffeoyl-olean-12-en-28-oic acid (29), and (23E)-coumaroylhederagenin (31) showed notable inhibitory effects on ATP-citrate lyase (ACL), with IC50 values of 3.6, 1.6, and 4.7 μM, respectively. Additionally, 3β-acetyl-ursolic acid (17) demonstrated dual inhibitory activity against both ACC1 and ACL, with IC50 values of 10.3 and 2.0 μM, respectively. The interactions of the active compounds with ACC1 and ACL enzymes were examined through molecular docking studies. From a chemotaxonomic perspective, the isolation of bis-iridoid glycosides in this study may aid in clarifying the taxonomic relationship between the genera Kolkwitzia and Lonicera within the Caprifoliaceae family. These findings highlight the importance of conserving plant species with unique and diverse secondary metabolites, which could serve as potential sources of new therapeutic agents for treating ACC1/ACL-associated diseases.

Tailored culture strategies to promote antimicrobial secondary metabolite production in Diaporthe caliensis: a metabolomic approach

BackgroundIn the search for new antimicrobial secondary metabolites of fungi, optimizing culture conditions remains a critical challenge, as standard laboratory approaches often result in low yields. While non-selective methods, such as modifying culture media, have been effective in expanding the chemical diversity of fungal metabolites, they have not yet established a direct link to key process parameters crucial for further optimization. This study investigates the capacity of Diaporthe caliensis as a biofactory for biologically active secondary metabolites, employing tailored culture media to explore the relationship between chemical diversity and critical process variables.ResultsThe metabolomic profiles, antibacterial activities, and production yields of the extracts were analyzed to progressively adjust the culture conditions. This study was conducted in five steps, evaluating carbon and nitrogen source concentration, nitrogen source type, salt supplementation, and pH adjustment. Altering the rice starch concentration affected biomass yield per unit of oxygen consumed, while modifications to the nitrogen source concentration influenced both the bioactivity and chemical space by Diaporthe caliensis. Despite changes at the metabolome level, the extracts consistently exhibited potent antibacterial activities, influenced by the nitrogen source, added salts and pH adjustments. For instance, when using corn steep liquor and rice starch, supplemented with micronutrients, different metabolites were produced depending on whether buffer or water was used, though both conditions showed similar antibacterial activities (IC50 ≈ 0.10 mg mL− 1 against Staphylococcus aureus and ≈ 0.14 mg mL− 1 against Escherichia coli). In the treatment where buffer was used to stabilize pH change, there was an increase in the production of phomol-like compounds which are associated with known antibiotic properties. In contrast, in the treatments using water, the drop in pH stimulated the production of previously unidentified metabolites with potential antimicrobial activity.ConclusionsThis study proposes a strategic methodology for the tailored formulation of culture media aiming to promote the biosynthesis of diverse secondary metabolites. This approach revealed the critical role of nutrient limitation and pH regulation in stimulating the production of polyketide-lactone derivatives, including the antibiotic phomol. Ultimately, the systematic, custom-designed culture conditions developed in this work offer a promising strategy for expanding the chemical diversity of Diaporthe caliensis, while providing valuable insights into the key parameters needed for optimizing this fungal biofactory.Graphical

Analysis of Chemical Traits of Pollen from Nine Ericaceous Species in Southwestern China

Chemical traits (primary and secondary metabolites) are important features of plants. An increasing number of studies have focused on the ecological significance of secondary metabolites in plant parts, especially in pollen. Ericaceae species exhibit significant morphological variations and diverse colors, are widely distributed throughout China and are popular ornamental garden plants. The chemical trait of pollen in Ericaceae species and their potential ecological significance remain unclear. We selected a total of nine Ericaceae species from three nature reserves in southwestern China, which were the predominant flowering Ericaceae plants for each site, and measured their floral characteristics, nectar volume and sugar concentration. We determined the types of pollinators of these species based on a literature review and used UPLC-QTOF-MS to analyze the types and relative contents of primary metabolites (amino acids and fatty acids) and secondary metabolites (terpenoids, phenolics and nitrogenous compounds) in the pollen and other tissues, including the stems, leaves, petals and nectar. The results showed that each species exhibited unique floral characteristics. Enkianthus ruber, Pieris formosa, Rhododendron agastum, R. irroratum, R. virgatum and R. rubiginosum were pollinated by bees, and R. delavayi, R. decorum and R. excellens were pollinated by diverse animals (bees, birds and Lepidoptera). The pollen of these Ericaceae species was rich in phenolics and terpenoids, especially flavonoids. Grayanotoxin, andromedotoxin and asebotin (toxic diterpene compounds) were also detected in the pollen of some of the Ericaceae species in our study, and their response value was low. The relative contents and diversity of secondary metabolites in the pollen were higher than those in the nectar but lower than those in the leaves, petals and stems. The five chemical compounds with the highest content (four flavonoids, one triterpene) in the pollen were also detected in the stems, leaves and petals, and the response value of most of these chemicals in pollen was not significantly correlated with that in other tissues. Rhododendron species has a closer relationship with chemical traits in pollen compared with Enkianthus and Pieris species. The response value of total secondary metabolites in the pollen of species pollinated only by bees was higher than that of species pollinated by diverse animals. Our research indicates that the pollen of ericaceous species contains a wide array of metabolites, establishing a foundation for advancing the nutritional potential of the pollen of horticultural ericaceous species and deepening our understanding of its chemical and ecological significance.

Beyond Essential Oils: Diterpenes, Lignans, and Biflavonoids from Juniperus communis L. as a Source of Multi-Target Lead Compounds.

Common Juniper (Juniperus communis L.) is a gymnosperm that stands out through its fleshy, spherical female cones, often termed simply "berries". The cone berries and various vegetative parts (leaves, twigs and even roots) are used in traditional phytotherapy, based on the beneficial effects exerted by a variety of secondary metabolites. While the volatile compounds of Juniperus communis are known for their aromatic properties and have been well-researched for their antimicrobial effects, this review shifts focus to non-volatile secondary metabolites-specifically diterpenes, lignans, and biflavonoids. These compounds are of significant biomedical interest due to their notable pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. The aim of this review is to offer an up-to-date account of chemical composition of Juniperus communis and related species, with a primary emphasis on the bioactivities of diterpenes, lignans, and biflavonoids. By examining recent preclinical and clinical data, this work assesses the therapeutic potential of these metabolites and their mechanisms of action, underscoring their value in developing new therapeutic options. Additionally, this review addresses the pharmacological efficacy and possible therapeutic applications of Juniperus communis in treating various human diseases, thus supporting its potential role in evidence-based phytotherapy.

Discovery of Alanomyces manoharacharyi: A Novel Fungus Identified Using Genome Sequencing and Metabolomic Analysis.

In this study, a new species of Alanomyces was isolated as an endophyte from the bark of Azadirachta indica from Mulshi, Maharashtra. The identity of this isolate was confirmed based on the asexual morphological characteristics as well as multi-gene phylogeny based on the internal transcribed spacer (ITS) and large subunit (LSU) nuclear ribosomal RNA (rRNA) regions. As this was the second species to be reported in this genus, we sequenced the genome of this species to increase our knowledge about the possible applicability of this genus to various industries. Its genome length was found to be 35.01 Mb, harboring 7870 protein-coding genes as per Augustus and 8101 genes using GeMoMa. Many genes were annotated using the Clusters of Orthologous Groups (COGs) database, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Swiss-Prot, NCBI non-redundant nucleotide sequences (NTs), and NCBI non-redundant protein sequences (NRs). The number of repeating sequences was predicted using Proteinmask and RepeatMasker; tRNA were detected using tRNAscan and snRNA were predicted using rfam_scan. The genome was also annotated using the Pathogen-Host Interactions Database (PHI-base) and AntiSMASH. To confirm the evolutionary history, average nucleotide identity (ANIb), phylogeny based on orthologous proteins, and single nucleotide polymorphisms (SNPs) were carried out. Metabolic profiling of the methanolic extract of dried biomass and ethyl acetate extract of the filtrate revealed a variety of compounds of great importance in the pharmaceutical and cosmetic industry. The characterization and genomic analysis of the newly discovered species Alanomyces manoharacharyi highlights its potential applicability across multiple industries, particularly in pharmaceuticals and cosmetics due to its diverse secondary metabolites and unique genetic features it possesses.

Recent Updates on the Secondary Metabolites from Fusarium Fungi and Their Biological Activities (Covering 2019 to 2024).

Fusarium species are commonly found in soil, water, plants, and animals. A variety of secondary metabolites with multiple biological activities have been recently isolated from Fusarium species, making Fusarium fungi a treasure trove of bioactive compounds. This mini-review comprehensively highlights the newly isolated secondary metabolites produced by Fusarium species and their various biological activities reported from 2019 to October 2024. About 276 novel metabolites were revealed from at least 21 Fusarium species in this period. The main metabolites were nitrogen-containing compounds, polyketides, terpenoids, steroids, and phenolics. The Fusarium species mostly belonged to plant endophytic, plant pathogenic, soil-derived, and marine-derived fungi. The metabolites mainly displayed antibacterial, antifungal, phytotoxic, antimalarial, anti-inflammatory, and cytotoxic activities, suggesting their medicinal and agricultural applications. This mini-review aims to increase the diversity of Fusarium metabolites and their biological activities in order to accelerate their development and applications.

Genomic insights into the cold adaptation and secondary metabolite potential of Pseudoalteromonas sp. WY3 from Antarctic krill.

In the Antarctic marine ecosystem, krill play a pivotal role, yet the intricate microbial community intertwined with these diminutive crustaceans remains largely unmapped. In this study, we successfully isolated and characterized a unique bacterial strain, Pseudoalteromonas sp. WY3, from Antarctic krill. Genomic analysis revealed that WY3 harbors a multitude of genes associated with cold shock proteins, oxidoreductases, and enzymes involved in the osmotic stress response, equipping it with a robust molecular arsenal to withstand frigid Antarctic conditions. Furthermore, the presence of two distinct biosynthesis-related gene clusters suggests that WY3 has the potential to synthesize diverse secondary metabolites, including aryl polyenes and ribosomally synthesized and post-translationally modified peptides. Notably, the identification of genes encoding enzymes crucial for biological immunity pathways, such as apeH and ubiC, hints at a complex symbiotic relationship between WY3 and its krill host. This comprehensive study highlights the robust potential of WY3 for secondary metabolite production and its remarkable ability to thrive at extremely low temperatures in the Antarctic ecosystem, shedding light on the interplay between culturable microorganisms and their hosts in harsh environments, and providing insights into the underexplored microbial communities associated with Antarctic marine organisms and their role in environmental adaptation and biotechnological applications.

Using metabolomics to explore the effects of epigenetic-modification strategies on the metabolites of Acanthus ilicifolius L. endophytic fungi against ovarian cancer

Ovarian cancer is a serious threat to women's health and safety. So far, people have discovered more than 130 small molecule compounds of natural origin for anti-tumor, of which approximately 50% are of microbial origin. The Acanthus ilicifolius L. species is primarily distributed in the Guangdong, Hainan, and Guangxi regions of China and grows in tidally accessible coastal areas. Recent studies have revealed that Acanthus ilicifolius L. extracts are endowed with a range of pharmacological properties, including anti-inflammatory, hepatoprotective, antioxidant, and antitumor activities. Endophytic fungi are commonly found in the healthy tissue and organs of medicinal plants. These fungi and the plants they inhabit form mutually beneficial symbiotic relationships. Endophytic fungi produce a series of secondary metabolites, with active substances having shown great economic value and applications prospects in drug research and development as well as for the biological control of plant diseases. Secondary metabolites production by endophytic fungi is regulated by specific gene clusters, and several techniques have been used to stimulate the secondary metabolic processes of fungi, including epigenetic-modification and OSMAC (one strain many compounds) strategies, co-culturing, and gene modification. Among these, epigenetic modification has been shown to be effective; this strategy involves the addition of small-molecule epigenetic modifiers to the culture medium, thereby activating silenced biosynthetic gene clusters without altering the DNA sequences of the fungi. This approach facilitates the expression of silenced genes in endophytic fungi, thereby increasing the number and diversity of secondary metabolites. Furthermore, it assists in overcoming the inhibition of microbial secondary-metabolite synthesis under laboratory conditions, and enhances silenced-gene expressions. The advent of novel analytical techniques and bioinformatics has provided a comprehensive, multifaceted, and holistic understanding of fungal metabolism through the development of metabolomics as a research platform. However, few studies have combined anti-ovarian cancer-activity screening with metabolomic approaches in the search for activity-differentiating metabolites from endophytic fungi under the intervention of epigenetic modifiers. Herein, we investigated the impact of epigenetic modifiers on the secondary metabolites of the endophytic Diaporthe goulteri fungus from Acanthus ilicifolius L. to determine their potential anti-ovarian cancer activities. Crude extracts were obtained by controlling three variables: the number of fermentation days, the type of epigenetic modifier, and its concentration, with activities screened using the CCK-8 (cell counting kit-8) method. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was subsequently employed for non-targeted metabolomic analysis. A multivariate statistical analysis model was constructed using principal component analysis and orthogonal partial least squares-discriminant analysis, which combines model and variable importance projection, with qualitative screening performed and significant changes (variable importance in the projection (VIP)≥1; P<0. 05) determined. Fifteen differential metabolites were identified in the fungal and epigenetic modification group, primarily comprising polyketides, amino acids, derivatives, alkaloids, and organic acids, including prenderol, glycine, valine, 2-ethylcaproic acid, rubratoxin B, finasteride, 6-silaspiro[5.5]undecane, 1-(2-nitrophenoxy)octane, heptadecene, 1-pentadecene, 11-ketoetiocholanolone, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, tabutrex, (3aR,6S,6aS)-6-(4-hydroxy-2-methoxy-2-butanyl)-4,4-dimethylhexahydro-1(2H)-pentalenone, and 8-aminoquinoline. The expressions of prenderol, 1-(2-nitrophenoxy)octane, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, and 8-aminoquinoline were downregulated, whereas the expressions of the remaining 10 substances were upregulated. Polyketides were the main components that exhibited higher expressions. This study showed that latent active differential metabolites can be searched by combining anti-ovarian cancer-activity screening with metabolomics analysis, thereby providing a reference for the further development of Acanthus ilicifolius L. resources and the subsequent targeted isolation of active compounds.

Phytochemical screening and evaluation of antiradical and antimicrobial activities of Annona senegalensis and Detarium microcarpum leaves used in Benin to treat urinary infections

The challenge of resistance to synthetic antimicrobials necessitates new alternative solutions. Medicinal plants are rich in active compounds with various medicinal properties that can be used in treatment of urinary infections. This work aims to highlight the value of Annona senegalensis and Detarium microcarpum by evaluating phytochemical and antimicrobial potentials of their leaf extracts. Qualitative and quantitative analyses were carried out using color and precipitation reactions and spectrophotometric assays. The antiradical activity was evaluated using the DPPH test, and the antimicrobial activity was assessed by the agar diffusion method. Phytochemical screening showed that both plants contain anthraquinones, catechic tannins, coumarins, flavonoids, reducing compounds, sterols and terpenes. Hydroethanolic extract of Detarium microcarpum and A. senegalensis showed IC50 inhibition percentages of 0.20 mg/mL and 0.22 mg/mL respectively. Regarding antimicrobial activity, the hydroethanolic leaf extracts of D. microcarpum and A. senegalensis were found to be bactericidal and fungicidal against the tested bacteria and molds. This extract showed more pronounced antimicrobial activity than amoxicillin and ciprofloxacin, which are synthetic antimicrobials. Diversity of secondary metabolites and notable antimicrobial activity of D. microcarpum and A. senegalensis may justify their use in traditional medicine for treating urinary infections in Benin.

Multi-omics analysis uncovers the transcriptional regulatory mechanism of magnesium Ions in the synthesis of active ingredients in Sophora tonkinensis

Magnesium (Mg) plays a pivotal role as an essential component of plant chlorophyll and functions as a critical coenzyme. However, research exploring the regulatory mechanisms of magnesium ions on the synthesis of secondary metabolites is still in its early stages. Sophora tonkinensis is a widely utilized medicinal plant in China, recognized for its diverse secondary metabolites with active properties. This study investigates variations in these ingredients in tissue-cultured seedlings under varying magnesium concentrations. Simultaneously, an omics data analysis was conducted on tissue-cultured seedlings subjected to treatments with magnesium and low magnesium. These comprehensive omics analyses aimed to elucidate the mechanisms through which magnesium influences active components, growth, and development. Magnesium exerts a pervasive influence on various metabolic pathways, forming an intricate network. Research findings indicate that magnesium impacts diverse metabolic processes, including the absorption of potassium and calcium, as well as photosynthetic activity. Consequently, these influences lead to discernible changes in the levels of pharmacologically active compounds and the growth and developmental status.This study is the first to employ a multi-omics data analysis in S. tonkinensis. This methodology allows us to uncover the overarching impact of metabolic networks on the levels of various active ingredients and specific phenotypes.

Research progress in isolation strategies and bioactive substances of microorganisms in extreme environments

Microbial resources are diverse and abundant, serving as a crucial source for the discovery of bioactive substances. However, as the research on microbial secondary metabolites deepens, discovering new microorganisms and novel bioactive secondary metabolites from conventional environments is becoming increasingly challenging. The microorganisms inhabiting extreme environments have unique physiological characteristics and can develop distinctive metabolic pathways, holding immense potential for producing chemically diverse and novel bioactive secondary metabolites. This article comprehensively overviews the recent advancements in the isolation strategies of microorganisms from extreme environments and the research progress in their bioactive substances, including antimicrobial, anticancer, and antioxidant compounds. This review aims to serve as a reference for the development and utilization and the related studies of the microbial resources in extreme environments.

Dodecanoyl-L-tryptophan: A Novel Natural Antibiotic Isolated from Mesophotic Sponge-associated Salinicola sp. LHM and its Biological Function

Background: Sponge-associated microbiota plays a crucial role in maintaining host health by providing chemical defense through the synthesis of diverse secondary metabolites. However, research on these secondary metabolites is still in its early stages. Objective: The present study aimed to investigate new natural antibiotics from mesophotic sponge symbiotic microbiota and explore its in vitro antibacterial activity and preliminary biological function. Methods: Bacteria strain Salinicola sp. LHM was isolated from sponge L. birotulata L26 and identified based on the 16S rRNA gene analysis. Subsequently, the strain was fermented using a liquid M9 medium and screened for antibiotics with an antibacterial guiding assay. Extensive chromatographic methods were introduced to isolate the target compound, and its chemical structure was elucidated by spectroscopic analysis (LC-MS, NMR). The minimum inhibitory concentration (MIC) and cytotoxicity experiments evaluated the isolated compound's biological activity. Furthermore, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quartz crystal microbalance with dissipation (QCM-D) were used to study the bactericidal mechanism of DLT. Finally, the preliminary biological function was explored by performing the cell-feeding experiment. Results: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. result: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. Conclusion: This research identified one novel natural antibiotic DLT and provided initial insights into the chemical defense exerted by Salinicola sp. LHM with its secondary metabolite DLT.

Discovery of a novel methionine biosynthetic route via O-phospho-l-homoserine.

Methionine (Met), a sulfur-containing amino acid, is essential for the underlying biological processes in living organisms. In addition to its importance as a starting building block for peptide chain elongation in protein biosynthesis, Met is a direct precursor of S-adenosyl-l-methionine, an indispensable methyl donor molecule in primary and secondary metabolism. Streptomyces bacteria are well known to produce diverse secondary metabolites, but many strains lack canonical Met pathway genes for l-homocysteine, a direct precursor of Met in bacteria, plants, and archaea. Here, we report the identification of a novel gene (metM) responsible for the Met biosynthesis in Streptomyces strains and demonstrate the catalytic function of the gene product, MetM. We further identified the metO gene, a downstream gene of metM, and showed that it encodes a sulfur-carrier protein (SCP). In in vitro analysis, MetO was found to play an important role in a sulfur donor by forming a thiocarboxylated SCP. Together with MetO (thiocarboxylate), MetM directly converted O-phospho-l-homoserine to l-homocysteine. O-Phospho-l-homoserine is also known as an intermediate for threonine biosynthesis in bacteria and plants, and MetM shares sequence homology with threonine synthase. Our findings thus revealed that MetM seizes O-phospho-l-homoserine from the threonine biosynthetic pathway and uses it as an intermediate of the Met biosynthesis to generate the sulfur-containing amino acid. Importantly, this MetM/MetO pathway is highly conserved in Streptomyces bacteria and distributed in other bacteria and archaea.IMPORTANCEMethionine (Met) is a sulfur-containing proteinogenic amino acid. Moreover, Met is a direct precursor of S-adenosyl-l-methionine, an indispensable molecule for expanding the structural diversity of natural products. Because Met and its derivatives benefit humans, the knowledge of Met biosynthesis is important as a basis for improving their fermentation. Streptomyces bacteria are well known to produce diverse and valuable natural products, but many strains lack canonical Met pathway genes. Here, we identified a novel l-homocysteine synthase (MetM) in Streptomyces and demonstrated that it converts O-phospho-L-homoserine to l-homocysteine using a thiocarboxylated sulfur-carrier protein as a sulfur donor. Since the metM is distributed in other bacteria and archaea, our pioneering study contributes to understanding Met biosynthesis in these organisms.

Investigation on taxonomy, secondary metabolites and antibacterial activity of Streptomyces sediminicola sp. nov., a novel marine sediment-derived Actinobacteria.

Marine actinomycetes, especially Streptomyces, are recognized as excellent producers of diverse and bioactive secondary metabolites on account of the multiplicity of marine habitations and unique ecological conditions, which are yet to be explored in terms of taxonomy, ecology, and functional activity. Isolation, culture and genome analysis of novel species of Streptomyces to explore their potential for discovering bioactive compounds is an important approach in natural product research. A marine actinobacteria, designated strain SCSIO 75703T, was isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity assays. The phylogenetic, phenotypic and chemotaxonomic analyses indicate that strain SCSIO 75703T represents a novel species in genus Streptomyces, for which the name Streptomyces sediminicola sp. nov. is proposed. Genome analysis revealed the presence of 25 secondary metabolite biosynthetic gene clusters. The screening for antibacterial activity reveals the potential to produce bioactive metabolites, highlighting its value for in-depth exploration of chemical constituents. Seven compounds (1-7) were separated from the fractions guided by antibacterial activities, including three indole alkaloids (1-3), three polyketide derivatives (4-6), and 4-(dimethylamino)benzoic acid (7). These primarily antibacterial components were identified as anthracimycin (4), 2-epi-anthracimycin (5) and β-rubromycin (6), presenting strong antibacterial activities against Gram-positive bacteria with the MIC value ranged from 0.125 to 16μg/mL. Additionally,, monaprenylindole A (1) and 3-cyanomethyl-6-prenylindole (2) displayed moderate inhibitory activities against α-glucosidase with the IC50 values of 83.27 and 86.21μg/mL, respectively. Strain SCSIO 75703T was isolated from marine sediment and identified as a novel species within the genus Streptomyces. Based on genomic analysis, compounds isolation and bioactivity studies, seven compounds were identified, with anthracimycin and β-rubromycin showing significant biological activity and promising potential for further applications.

Are there conserved biosynthetic genes in lichens? Genome-wide assessment of terpene biosynthetic genes suggests ubiquitous distribution of the squalene synthase cluster

Lichen-forming fungi (LFF) are prolific producers of functionally and structurally diverse secondary metabolites, most of which are taxonomically exclusive and play lineage-specific roles. To date, widely distributed, evolutionarily conserved biosynthetic pathways in LFF are not known. However, this idea stems from polyketide derivatives, since most biochemical research on lichens has concentrated on polyketide synthases (PKSs). Here, we present the first systematic identification and comparison of terpene biosynthetic genes of LFF using all the available Lecanoromycete reference genomes and 22 de novo sequenced ones (111 in total, representing 60 genera and 23 families). We implemented genome mining and gene networking approaches to identify and group the biosynthetic gene clusters (BGCs) into networks of similar BGCs. Our large-scale analysis led to the identification of 724 terpene BGCs with varying degrees of pairwise similarity. Most BGCs in the dataset were unique with no similarity to a previously known fungal or bacterial BGC or among each other. Remarkably, we found two BGCs that were widely distributed in LFF. Interestingly, both conserved BGCs contain the same core gene, i.e., putatively a squalene/phytoene synthase (SQS), involved in sterol biosynthesis. This indicates that early gene duplications, followed by gene losses/gains and gene rearrangement are the major evolutionary factors shaping the composition of these widely distributed SQS BGCs across LFF. We provide an in-depth overview of these BGCs, including the transmembrane, conserved, variable and LFF-specific regions. Our study revealed that lichenized fungi do have a highly conserved BGC, providing the first evidence that a biosynthetic gene may constitute essential genes in lichens.

Chemical constituents from a soil fungus Xylaria sp. Y01 and their anticancer potential

Fifteen compounds, namely three new cytochalasans, one new sesquiterpenoid, two new amides, eight known cytochalasans, and one known amide, were isolated from the rice medium fermented by a soil fungus Xylaria sp. Y01. The structures of these compounds were determined through comprehensive analyses of their extensive spectroscopic data, along with quantum chemical calculations. In vitro cytotoxicity assays, we selected three cancer cell lines (HCT116, 4T1, and MHCC97H) and one normal human gastric epithelial GES-1 cell line to explore their potential as anticancer agents. As a result, 6,7-dihydro-7-oxo-cytochalasin C, 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C, 19,20-epoxycytochalasin D, and 19‑epi-cytochalasin P1 showed cytotoxicity against GES-1, while only 19,20-epoxycytochalasin D also exhibited cytotoxicity against 4T1. Our findings further enrich the structural diversity of secondary metabolites from Xylaria species and provide clues for exploring their anticancer potential.

Comparative Transcriptomics Revealed Physalis floridana Rydb. Influences on the Immune System of the 28-Spotted Ladybird Beetle (Henosepilachna vigintioctopunctata)

Physalis floridana Rydb., a member of the Solanaceae family, is renowned for its diverse secondary metabolites, including physalins and withanolides. The 28-spotted ladybird beetle (Henosepilachna vigintioctopunctata) is a notorious pest severely damaging Solanaceous crops. This study demonstrates that P. floridana Rydb. significantly impacts on the development and reproductive suppression of H. vigintioctopunctata. A comparative transcriptome analysis was performed by feeding H. vigintioctopunctata larvae on P. floridana Rydb., Solanum nigrum L., Solanum tuberosum L., and Solanum lycopersicum L. The results reveal that larvae fed on P. floridana Rydb. exhibit numerous differentially expressed genes, which are notably enriched in pathways related to energy metabolism, immunity, and detoxification. These functions and pathways are less enriched in larvae fed by other hosts. Weighted Gene Co-expression Network Analysis (WGCNA) indicates that feeding on P. floridana Rydb. influences the expression of specific genes involved in the Toll and IMD signaling pathways, impacting the immune system of H. vigintioctopunctata larvae. This study provides transcriptomic insights into larval responses to different diets and suggests that the effect of P. floridana Rydb. on the immune system of H. vigintioctopunctata is a key defense mechanism against herbivores.

1-Acetyl-β-Carboline from a Jeju Gotjawal Strain Lentzea sp. JNUCC 0626 and Its Melanogenic Stimulating Activity in B16F10 Melanoma Cells.

The genus Lentzea is a prolific source of bioactive and structurally diverse secondary metabolites. We isolated a novel strain, Lentzea sp. JNUCC 0626, from Hwasun Gotjawal on Jeju Island, Korea. Based on 16S rRNA partial gene sequence analysis, strain JNUCC 0626 is closely related to Lentzea isolaginshaensis NX62 (99.41% similarity), Lentzea pudingi DHS C021 (99.31%), and Lentzea cavernae SYSU K10001 (99.26%). From the fermentation broth of JNUCC 0626, we isolated 1-acetyl-β-carboline, whose structure was established using IR, HR-ESI-MS, and 1D- and 2D-NMR techniques. 1-acetyl-β-carboline was found to activate melanogenesis in mouse B16F10 cells without cytotoxicity at concentrations up to 50 μM. At this concentration, the compound increased melanin content by 27.44% and tyrosinase activity by 240.64% compared to the control, by upregulating key melanogenic enzymes, including tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF), a central regulator of melanogenesis. In addition, 1-acetyl-β-carboline significantly inhibited ERK phosphorylation, reducing it by 20.79% at a concentration of 12.5 μM and by 25.63% at 25 μM. This inhibition supports the hypothesis that 1-acetyl-β-carboline enhances melanin synthesis by upregulating MITF and melanogenic enzymes via the ERK signaling pathway. This study aimed to isolate and identify 1-acetyl-β-carboline from a novel strain of Lentzea sp. JNUCC 0626, discovered in Gotjawal, Jeju Island, and to evaluate its effect on melanin production in B16F10 melanoma cells. Skin irritation tests on 32 subjects confirmed its safety for topical use, and the findings suggest that 1-acetyl-β-carboline, which enhances melanogenesis without cytotoxicity, holds promise as a therapeutic agent for hypopigmentation-related conditions or as a cosmetic ingredient.

Chemical composition of γ-irradiated German chamomile (Matricaria recutita L.) flower essential oils, acetylcholinesterase inhibitory activity and effects on growth inhibition of Staphylococcus aureus and Candida albicans

Radiation-induced mutations have been the most commonly used technique for the development of mutant varieties. The primary aim has been to upgrade the existing plant varieties by varying a few major traits responsible for limiting metabolite productivity. The increasing regulations on protected plant varieties and germplasms have restricted their use. The induced mutants have played a vital role in strengthening the plant breeding program. The medicinal and aromatic plants have been poorly explored for mutation breeding. CSIR-CIMAP has initiated a mutation breeding program on some of the high-value plants, like Matricaria. As a result, we could develop gamma-rays-induced stable accessions. Genus Matricaria is well known for the biosynthesis of diverse bioactive plant secondary metabolites as well as for its traditional and healthcare benefits documented in Ph. Eur. In the present work, gamma-irradiated stable accessions of German chamomile, Matricaria recutita L., have been investigated for their essential oil composition and biological assessment. After a thorough investigation for a two-year cropping period, we have observed that some accessions contain the highest α-bisabolol oxide B proportions (24.3–55.3%), while quite a few showed chamazulene (2.9–5.8%), α-bisabolone oxide A (6.5–38%), and α-bisabolol oxide A (30.1–55.3%). A few accessions were marked by the presence of lavandulol, an irregular monoterpenoid of high fragrance value. The antibacterial, anti-inflammatory, and acetylcholinesterase (AChE) inhibitory properties of these gamma-irradiated accessions were also evaluated. The accessions G6-R5-5 and G2-R1-6 exhibited maximum inhibition against S. aureus whereas G2-R1-1 arrested the growth of C. albicans. Furthermore, G2R1-3 composition is responsible for reducing AChE and inflammation in cell lines. These results may open up ways to develop plant-derived consumer products from Matricaria recutita L.