Source Of Natural Products Research Articles

Antimicrobial and quorum sensing inhibitory activity of epiphytic bacteria isolated from the red alga Halymenia durvillei.

Halymenia durvillei is a red alga that is commonly utilized in the Philippines as food and as a source of high-value natural products for industrial applications. However, there are no studies regarding the microbial community associated with H. durvillei and its potential applications. This study aimed to isolate and identify the epiphytic bacteria of H. durvillei and determine their antimicrobial and quorum sensing inhibitory (QSI) effects. The thalli of H. durvillei were collected at the shores of Santa Fe, Bantayan, Cebu, Philippines. Bacterial isolates were identified using 16S rRNA, and their ethyl acetate (EtOAc) extracts were subjected to antimicrobial susceptibility tests against representative species of yeast and Gram-negative and Gram-positive bacteria. Their QSI activity against Chromobacterium violaceum was also determined. Fourteen distinct bacterial colonies belonging to four genera, namely Alteromonas (3), Bacillus (5), Oceanobacillus (1) and Vibrio (5), were successfully isolated and identified. All 14 bacterial isolates exhibited antibacterial effects. EPB9, identified as Bacillus safensis , consistently showed the strongest inhibition against Escherichia coli , Staphylococcus aureus and Staphylococcus epidermidis , with minimum inhibitory concentrations (MICs) ranging from 0.0625 to 1.0 mg ml-1. In contrast, all 14 isolates showed weak antifungal effects. Both B. safensis (EPB9) and Bacillus australimaris (EPB15) exhibited QSI effects at 100 mg ml-1, showing opaque zones of 3.1±0.9 and 3.8±0.4 mm, respectively. This study is the first to isolate and identify the distinct microbial epiphytic bacterial community of H. durvillei and its potential as an abundant resource for new antibacterial and QSI bioactives.

Chemical constituents from the medicinal herb-derived fungus Chaetomium globosum Km1226

BackgroundEndophytic fungi have proven to be a rich source of novel natural products with a wide-array of biological activities and higher levels of structural diversity.ResultsChemical investigation on the liquid- and solid-state fermented products of Chaetomium globosum Km1226 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1–14. Their structures were determined by spectroscopic analysis as three previously undescribed C13-polyketides, namely aureonitol C (1), mollipilins G (2), and H (3), along with eleven known compounds 4–14. Among these, mollipilin A (5) exhibited significant nitric oxide production inhibitory activity in LPS-induced BV-2 microglial cells with an IC50 value of 0.7 ± 0.1 µM, and chaetoglobosin D (10) displayed potent anti-angiogenesis property in human endothelial progenitor cells (EPCs) with an IC50 value of 0.8 ± 0.3 µM.ConclusionsThree previously unreported compounds 1–3 were isolated and identified. Mollipilin A (5) and chaetoglobosin D (10) could possibly be developed as anti-inflammatory and anti-angiogenic lead drugs, respectively.

ABC-HuMi: the Atlas of Biosynthetic Gene Clusters in the Human Microbiome.

The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at https://www.ccb.uni-saarland.de/abc_humi/.

Evaluation of Antimicrobial Potential of Endophytic Fungi and GC-MS Metabolic Profiling of Cephalosporium sp., and Fusarium moniliforme

From last few decades, microbes gained special attention residing inside plant tissues, now called endophyte. Studies proved that these microbes are able to produce biologically active metabolites and effective candidates against various pathogens. Endophytic fungi are a source of natural therapeutic products. Therefore, endophytic Fusarium species are isolated from different plants. These endophytic Fusarium species showed a potential against common laboratory bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and Bacillus subtilis). Fusarium moniliforme and Cephalosporium sp., were further selected to isolate compounds by GC-MS techniques. The mycelial extract of Cephalosporium sp., and oily fraction of filtrates of F. moniliforme revealed the presence of several therapeutic compounds based on the peak areas, molecular weights, Rt (retention times) and m/z (mass fragmentations). The major bioactive metabolites identified from these fungi are Cholest-22-ene-21-ol, 3,5-dehydro-6-methoxy-pivalate, Salicylamide, 1,2-Benzenedicarboxylic acid, Geranyl isovalerate, and diisooctyl ester, and reported to possess antibacterial, antioxidant, nematicidal, and antifungal potential. These results will lead to further in-depth research into the potential cause of plants endophytes interactions. The wide application of fungal origin bio products offers an effective prospect for discovering novel therapeutic agents in order to combat infectious agents as well as agricultural pests.

Exploring the known chemical space of the plant kingdom: insights into taxonomic patterns, knowledge gaps, and bioactive regions

Plants are one of the primary sources of natural products for drug development. However, despite centuries of research, only a limited region of the phytochemical space has been studied. To understand the scope of what is explored versus unexplored in the phytochemical space, we begin by reconstructing the known chemical space of the plant kingdom, mapping the distribution of secondary metabolites, chemical classes, and plants traditionally used for medicinal purposes (i.e., medicinal plants) across various levels of the taxonomy. We identify hotspot taxonomic clades occupied by a large proportion of medicinal plants and characterized secondary metabolites, as well as clades requiring further characterization with regard to their chemical composition. In a complementary analysis, we build a chemotaxonomy which has a high level of concordance with the taxonomy at the genus level, highlighting the close relationship between chemical profiles and evolutionary relationships within the plant kingdom. Next, we delve into regions of the phytochemical space with known bioactivity that have been used in modern drug discovery. While we find that the vast majority of approved drugs from phytochemicals are derived from known medicinal plants, we also show that medicinal and non-medicinal plants do not occupy distinct regions of the known phytochemical landscape and their phytochemicals exhibit properties similar to bioactive compounds. Moreover, we also reveal that only a few thousand phytochemicals have been screened for bioactivity and that there are hundreds of known bioactive compounds present in both medicinal and non-medicinal plants, suggesting that non-medicinal plants also have potential therapeutic applications. Overall, these results support the hypothesis that there are many plants with medicinal properties awaiting discovery.

Tumebacillus lacus sp. nov., isolated from lake water.

A Gram-stain-positive, aerobic, rod-shaped, endospore-forming and motile, by means of peritrichous flagella, bacterium, designated DT12T, was isolated from a lake water sample from Datun Lake of Yunnan Province, PR China. The results of phylogenetic analysis based on 16S rRNA gene sequence and the concatenated alignment of 120 ubiquitous single-copy proteins indicated that the novel strain represented a member of the genus Tumebacillus. The sole quinone was menaquinone-7 and the cell-wall peptidoglycan was type-A1γ. The major fatty acids (>10 %) of the novel strain were iso-C15 : 0 and anteiso-C15 : 0, while the major polar lipids were phosphatidylmonomethylethanolamine, phosphatidylethanolamine and phosphatidylglycerol. The results of phylogenetic analyses combined with phylogenetic, phenotypic and chemotaxonomic features, strongly supported the hypothesis that the strain should be classified as representing a novel species of the genus Tumebacillus, for which the name Tumebacillus lacus sp. nov. is proposed. The type strain is DT12T (=KCTC 33958T= MCCC 1H00320T). The genomic analysis revealed that DT12T has various biosynthetic gene clusters for secondary metabolites, and members of the genus Tumebacillus may represent a promising source of new natural products. Our study also showed that members of the genus Tumebacillus are widely distributed in a variety of habitats throughout the globe, particularly in soils, human-, animal- and plant-associated environments. Members of the genus Tumebacillus may have an important role in the growth and health of humans, plants and animals.

Antimicrobial Potential of an Actinomycete Gordonia terrae JSN1.9-Derived Orange Pigment Extract

Actinomycetes are known to be a source of natural products and drugs. Gordonia terrae, an actinomycete pigment producer, shows potential in producing pigment with antimicrobial activity. This study aims to determine the antimicrobial activity of the active pigment fraction produced by the actinomycete G. terrae, assess the effects of the active pigment fraction on microbial cells, and identify the types of compounds present in the fraction. The pigment extract exhibited antimicrobial activity against Gram-positive bacteria and fungi. Specifically, it showed activity against Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25293, and Candida albicans ATCC 10231. Furthermore, the study evaluated the antimicrobial activities of the active fractions, revealed the active fraction had better antimicrobial activity than the crude extract. Scanning electron microscopy (SEM) confirmed that the active fraction of the pigment causes damage to B. subtilis ATCC 6633 cells, inhibits the formation of filaments in C. albicans ATCC 10231, and alters the normal shape of the cells. LC-MS/MS results showed that the active fraction contained several compounds known for their antimicrobial activity. Among the dominant compounds identified were cholestyramine, aminopregnane, and sphinganine. Thus, this study demonstrated that the orange pigment extract derived from G. terrae JSN1.9 exhibits promising antimicrobial activity.

Comprehensive Ethnomedicinal, Pharmacological and Phytochemical Report on <i>Basella alba</i> L. (Basellaceae)

From the primitive era to the current generation, natural extracts or products played the most conservative therapeutic and nutritional resources. Starting from the era of folklore or ancient, mother nature has protected us from various diseases by producing various natural products having strong medicinal implications like quinine, taxol, vinblastine, etc. Among the many available sources of natural products, pharma-herb being a new member has drawn considerable attention of the researcher in order to have a new pool of products having pronounced pharmaceutical activity. Now Basella alba is one of the brightest candidates belonging to pharma-herb because of its considerably enriched pharmacologically important product stocks like vitamin C, flavonoid compounds, carotenoids, saponins as well as a large number of different minerals and numerous amino acids. This plant is a perennial vine that is often cultivated as a food crop during the cooler months. It is also able to grow very fast and can resist temperatures that are quite high. Basella alba has been referred to by a number of different names throughout history, including Indian-, Malabar-, climber-, Ceylon-, and vine-spinach. Poi is the term that the majority of people in India use when referring to it. The various natural products isolated from B. alba have significant medicinal utilization because of its antimicrobial, anti-ulcer, wound healing, antiviral, anti- inflammatory depressant, androgenic potential, hepatoprotective, antidiabetic, antioxidant, anti-anxiety, diuretic and antiurolithiatic activities. This review will cover a detailed journey about Basella alba L. ranging from phytochemical to toxicological, morphological, pharmacological as well as medicinal importance.

Marine Fungi: A Prosperous Source of Novel Bioactive Natural Products.

As the number of viruses, bacteria, and tumors that are resistant to drugs continues to rise, there is a growing need for novel lead compounds to treat them. Marine fungi, due to their unique secondary metabolic pathways and vast biodiversity, have become a crucial source for lead compounds in drug development. This review utilizes bibliometric methods to analyze the research status of natural products from marine fungi in the past decade, revealing the hotspots and trends in this field from Web of Science database. Furthermore, this review summarizes the biological activities and effects on molecular mechanisms of novel natural compounds isolated from marine fungi in the past five years. These novel compounds belong to six different structural classes, such as alkaloids, terpenoids, anthraquinones, polyketones, etc. They also exhibited highly potent biological properties, including antiviral, antitumor, antibacterial, antiinflammatory, and other properties. This review demonstrates the hotspots and trends of marine fungi research in recent years, as well as the variety of chemical structure and biological activities of their natural products, and it may provide guidance for those interested in discovering new drugs from marine fungi and specific targeting mechanisms.

Emericellopsis maritima and Purpureocillium lilacinum Marine Fungi as a Source of Functional Fractions with Antioxidant and Antitumor Potential in Colorectal Cancer: A Preliminary Study

The marine environment is a promising source of natural products with possible pharmacological applications. In this sense, marine microorganisms, especially marine fungi, can produce bioactive compounds with various therapeutic properties. Colorectal cancer (CRC) represents a major health problem worldwide, since the treatments used to date are not capable of improving patient survival; that is why natural compounds from marine fungi offer a promising alternative. This study focused on evaluating the antitumor and antioxidant activity of fractions derived from the marine fungi E. maritima and P. lilacinum in two CRC cell lines T84 and SW480. Fractions Fr-EM6, Fr-EM7, Fr-EM8 and Fr-PLMOH-3 demonstrated potent cytotoxic activity in tested CRC cell lines with no activity in the non-tumor line. In particular, the Fr-PLMOH-3 fraction from P. lilacinum showed significant antiproliferative effects on T84 and SW480 cell lines and exhibited a greater cytotoxic effect on cancer stem cells compared to tumor cells. Furthermore, the Fr-EM8 fraction from E. maritima demonstrated a strong antioxidant capacity. These findings highlight the potential of compounds of marine origin as effective and selective antitumor agents for the treatment of CRC. Further studies are needed to explore the underlying mechanisms and potential clinical applications of these bioactive fractions and compounds.

Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial-mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development. Despite advancements in CDK5-targeted inhibitor research, the range of compounds available for clinical and preclinical trials remains limited. The marine environment has emerged as a prolific source of diverse natural products with noteworthy biological activities, including anti-cancer properties. In this study, we screened a library of 47,450 marine natural compounds from the comprehensive marine natural product database (CMNPD) to assess their binding affinity with CDK5. Marine compounds demonstrating superior binding affinity compared to a reference compound were identified through high-throughput virtual screening, standard precision and extra-precision Glide docking modes. Refinement of the selected molecules involved evaluating molecular mechanics-generalized born surface area (MM/GBSA) free binding energy. The three most promising compounds, (excoecariphenol B, excoecariphenol A, and zyzzyanone B), along with the reference, exhibiting favorable binding characteristics were chosen for molecular dynamics (MD) simulations for 200 nanoseconds. These compounds demonstrated interaction stability with the target during MD simulations. The marine compounds identified in this study hold potential as effective CDK5 inhibitors and warrant subsequent experimental validation.

Genus Litophyton: A Hidden Treasure Trove of Structurally Unique and Diversely Bioactive Secondary Metabolites.

Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.

Streptomyces rugosispiralis sp. nov., a Novel Actinobacterium Isolated from Peat Swamp Forest Soil That Produces Ansamycin Derivatives and Nocardamines.

Actinomycetes, especially the genus Streptomyces, are one of the most promising sources of bioactive natural products. In this study, a novel Streptomyces strain, RCU-064T, was isolated from a soil sample collected from a peat swamp forest in Thailand. Strain RCU-064T showed the highest 16S rRNA gene sequence similarity (99.06%) with Streptomyces malaysiensis NBRC 16446T. Based on a polyphasic approach, strain RCU-064T represents a novel species of the genus Streptomyces, for which the name Streptomyces rugosispiralis sp. nov. is proposed. The chemical isolation of the crude ethyl acetate extracts of the strain led to the isolation of six compounds: (1) geldanamycin, (2) 17-O-demethylgeldanamycin, (3) reblastatin, (4) 17-demethoxyreblastatin, (5) nocardamine, and (6) dehydroxynocardamine. These compounds were evaluated for their biological activities. All compounds showed no antimicrobial activity against tested microorganisms used in this study. Compounds (1)-(4) displayed cytotoxic activity against the NCI-H187 cell line, with IC50 values ranging from 0.045-4.250 µg/mL. Cytotoxicity against the MCF-7 cell line was found in compounds (1) and (3) with IC50 values of 3.51 and 1.27 µg/mL, respectively. Compounds (5) and (6) exhibited cytotoxicity only against Vero cells (IC50 of 16.57 µg/mL) and NCI-H187 cells (IC50 of 13.96 µg/mL), respectively. These results indicate that peat swamp forest soil remains a promising reservoir of novel actinomycetes capable of producing bioactive natural products.

Traditional Indian Medicinal Plants for the Treatment of Psoriasis: A Review of Active Constituents and their Pharmacological Effects

Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. The use of natural products for the treatment of psoriasis has gained interest due to their potential to modulate the immune system and reduce inflammation. Traditional Indian medicinal plants offer a promising source of natural products for the treatment of psoriasis. This article provides a comprehensive review of Indian medicinal plants that have been traditionally used for the treatment of psoriasis, along with their active constituents and reported pharmacological activities. In addition, we discuss the molecular pharmacology of psoriasis and the limitations of current allopathic treatment methods. Finally, we highlight the potential therapeutic effects of individual active constituents found in Indian medicinal plants, with a focus on their anti-inflammatory, antioxidant, and immunomodulatory properties. This review provides a basis for further research on the use of traditional Indian medicinal plants for the treatment of psoriasis.

Chromatography fractions from the ethyl acetate fraction of Harungana madagascariensis Lam. Ex Poiret fruits (Hypericaceae) inhibited the growth of Mycobacterium tuberculosis

The economic burden of drug resistant tuberculosis strain is enormous due to its being one of the leading cause of global mortality. New treatments that are faster, simpler and affordable are urgently needed. Thus this research aimed to validate that the ethyl acetate fraction from the Nigeria variety of Harungana madagascariensis contain secondary metabolites with anti-Mycobacterium tuberculosis activity. The fruit of H. madagascariensis was extracted with 70% aqueous ethanol by cold maceration. The crude aqueous ethanol extract was defatted with n-hexane by partitioning and the aqueous portion further partitioned with ethyl acetate to give ethyl acetate portion (EAP) used in this study. Fractionation of EAP was done using chromatographic techniques. Phytochemical screening of the fractions was done using standard methods. Anti- Mycobacterium tuberculosis screening was done using Lowestein Jensen(LJ) method (test fractions stock solution 1mg/ml diluted to a 0.01mg/ml in the LJ medium while isoniazid, dihydrostreptomycin, ethambutol and rifampicin at their reported minimum inhibition concentrations(MIC) were used as reference anti-TB drugs). Four (4) chromatography fractions (EAF1 –EAF4) were obtained. All fractions were found to contain phenolics with anthraquinone present in EAF2 and EAF3. Fractions EAF3 and EAF4 inhibited the growth of the Mycobacteria tuberculosis. This preliminary screening validates the use of H. madagascariensis in traditional medicine and as a potential source of natural products with anti-Mycobacterium tuberculosis activity as well as a good source of anthraquinone.

Advances of phytotherapy in ischemic stroke targeting PI3K/Akt signaling.

The pathogenesis of ischemic stroke is complex, and PI3K/Akt signaling is considered to play a crucial role in it. The PI3K/Akt pathway regulates inflammation, oxidative stress, apoptosis, autophagy, and vascular endothelial homeostasis after cerebral ischemia; therefore, drug research targeting the PI3K/Akt pathway has become the focus of scientists. In this review, we analyzed the research reports of antiischemic stroke drugs targeting the PI3K/Akt pathway in the past two decades. Because of the rich sources of natural products, increasing studies have explored the value of natural compounds, including Flavonoids, Quinones, Alkaloids, Phenylpropanoids, Phenols, Saponins, and Terpenoids, in alleviating neurological impairment and achieved satisfactory results. Herbal extracts and medicinal formulas have been applied in the treatment of ischemic stroke for thousands of years in East Asian countries. These precious clinical experiences provide a new avenue for research of antiischemic stroke drugs. Finally, we summarize and discuss the characteristics and shortcomings of the current research and put forward prospects for further in-depth exploration.

In vitro antioxidant, antiglycation, α-glucosidase and α-amylase inhibitory activities of extracts and solvent fractions of Elaeocarpus serratus L.

Plants are an essential source of unique pharmacologically active natural products beneficial to human and animal health. In this research, crude extracts and solvent fractions from the leaves, bark, stem, seeds and fruit pulp of Elaeocarpus serratus (Cylon olive) were assessed for their antioxidant potential, antiglycation and enzymatic inhibitory activity. Phytochemical contents were analyzed by the colorimetric method. Antioxidant activities were estimated by DPPH radical scavenging, superoxide anion radical and ferrous ion chelating assays. Antiglycation properties were determined through the bovine serum albumin-methylglyoxal (BSA-MG) test and enzyme inhibitory activities were tested in vitro on α-glucosidase and α-amylase. The ethyl acetate fraction of the leaves exhibited high phenolic content (71.63 ± 0.01 mg GAE/g DW). The n-butanol fraction of the bark had high flavonoid content (37.37 ± 0.07 mg QE/g DW). The n-butanol fraction of the bark also significantly inhibited both α-glucosidase and α-amylase with IC50 values of 2.32 ± 0.62, and 2.81 ± 0.37 μg/mL, respectively, compared with quercetin (43.27 ± 3.24 μg/mL) and acarbose (17.72 ± 2.35 μg/mL). These findings indicate that E. serratus can be a source of plant-based pharmaceuticals and natural products, which may be considered for the treatment of diabetes and the formulation of healthy food supplements. However, further studies are required on the isolation, identification and toxicity of components from E. serratus.

Phytochemical, antileishmanial, antifungal and cytotoxic profiles of Thymelaea tartonraira (L.) All. extracts

Extracts from leaves and stems of Thymelaea tartonraira (L.) All. growing in Tunisia were characterised for the presence of flavonoids and phenolic acids by LC-ESI-MS analysis. Twelve flavonoids and ten phenolic acids were detected for the first time in the aerial parts of this plant species, the most abundant compounds being gallic acid, kaempferol, catechin, chlorogenic acid, naringenin and acacetin. The extracts were subjected to in vitro antileishmanial, antifungal and cytotoxic assays, showing promising antileishmanial activity for the E6 dichloromethane extract from the stems (IC50 values of 1.12 ± 0.50 and 5.41 ± 1.84 µg/mL on L. donovani axenic and intramacrophagic amastigotes, respectively) at the level of the reference drug miltefosine for axenic model. No antifungal activity was observed against Candida albicans (CAAL) and Aspergillus fumigatus (ASFU) strains, with the exception of the E6 dichloromethane extract (IC50 value of 25.28 ± 4.89 µg/mL on CAAL93 strain). Low toxicity was also highlighted against macrophages Raw 264.7 cells. These promising results point out Thymelaea tartonraira (L.) All. extracts as a valuable source of new natural products to combat leishmaniasis.

Flux balance analysis-based metabolic modeling of microbial secondary metabolism: Current status and outlook.

In microorganisms, different from primary metabolism for cellular growth, secondary metabolism is for ecological interactions and stress responses and an important source of natural products widely used in various areas such as pharmaceutics and food additives. With advancements of sequencing technologies and bioinformatics tools, a large number of biosynthetic gene clusters of secondary metabolites have been discovered from microbial genomes. However, due to challenges from the difficulty of genome-scale pathway reconstruction and the limitation of conventional flux balance analysis (FBA) on secondary metabolism, the quantitative modeling of secondary metabolism is poorly established, in contrast to that of primary metabolism. This review first discusses current efforts on the reconstruction of secondary metabolic pathways in genome-scale metabolic models (GSMMs), as well as related FBA-based modeling techniques. Additionally, potential extensions of FBA are suggested to improve the prediction accuracy of secondary metabolite production. As this review posits, biosynthetic pathway reconstruction for various secondary metabolites will become automated and a modeling framework capturing secondary metabolism onset will enhance the predictive power. Expectedly, an improved FBA-based modeling workflow will facilitate quantitative study of secondary metabolism and in silico design of engineering strategies for natural product production.

From Threat to Opportunity: Harnessing the Invasive Carpobrotus edulis (L.) N.E.Br for Nutritional and Phytotherapeutic Valorization Amid Seasonal and Spatial Variability.

Carpobrotus edulis (L.) N.E.Br. (Hottentot-fig) is a problematic invasive species found in coastal areas worldwide. Mechanical removal is a common control method, leaving the removed biomass available as a possible source of natural phytochemicals with prospective commercial applications. While the Hottentot-fig's vegetative organs have been studied previously, this work establishes for the first time a seasonal and spatial comparative analysis of its nutritional, chemical, and bioactivity profiles (in three locations over four seasons). Proximate and mineral contents were assessed, along with its phenolic composition and in vitro antioxidant and anti-inflammatory properties. Hottentot-fig's biomass offered a good supply of nutrients, mainly carbohydrates, proteins, and minerals, with a tendency for higher concentrations of the most relevant minerals and proteins in autumn and winter, and in plants from sites A (Ria de Alvor lagoon) and B (Ancão beach). The extracts were rich in polyphenolics, with higher levels in spring and summer, especially for luteolin-7-O-glucoside and salicylic and coumaric acids. The extracts were also effective antioxidants, with stronger radical scavenging activities in spring and summer, along with anti-inflammatory properties. Our results suggest that the usually discarded plant material of this invasive halophyte could be valuable as a source of natural products with potential biotechnological applications in the food and nutraceutical industries.