Spectrum Of Secondary Metabolites Research Articles

Plant-derived bioactive compounds as key players in the modulation of immune-related conditions

AbstractThe immune system is a complex and fundamental network for organism protection. A minimal unbalance in the host defense system homeostasis can originate severe repercussions in human health. Fundamentally, immune-related diseases can arise from its compromise (immunodeficiency diseases), overactivation against itself (autoimmune diseases) or harmless substances (allergies), and failure of eliminating the harmful agent (chronic inflammation). The notable advances and achievements in the immune system diseases pathophysiology have been allowing for a dramatic improvement of the available treatments. Nevertheless, they present some drawbacks, including the inappropriate benefit/risk ratio. Therefore, there is a strong and urgent need to develop effective therapeutic strategies. Nature is a valuable source of bioactive compounds that can be explored for the development of new drugs. Particularly, plants produce a broad spectrum of secondary metabolites that can be potential prototypes for innovative therapeutic agents. This review describes the immune system and the inflammatory response and examines the current knowledge of eight plants traditionally used as immunomodulatory medicines (Boswellia serrata, Echinacea purpurea, Laurus nobilis, Lavandula angustifolia, Olea europaea, Salvia officinalis, Salvia rosmarinus, and Taraxacum officinale). Moreover, the issues responsible for possible biologic readout inconsistencies (plant species, age, selected organ, developmental stage, growth conditions, geographical location, drying methods, storage conditions, solvent of extraction, and extraction method) will also be discussed. Furthermore, a detailed list of the chemical composition and the immunomodulatory mechanism of action of the bioactive compounds of the selected plant extracts are presented. This review also includes future perspectives and proposes potential new avenues for further investigation.

A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Key role of phenol enzymes metabolism in the legume-rhizobial symbiosis under different water supply regimes

The legume-rhizobium interaction induces formation of specific reactions that take metabolism in the host plant up to a new functional level, increasing its tolerance to unfavourable cultivation conditions. Our objective was to study the participation of key enzymes – phenylalanine ammonia lyase, guaiacol peroxidase, and polyphenol oxidases – in the phenol-metabolism processes and synthesis of a broad spectrum of secondary metabolites in soybean plants that have established symbiotic interactions with rhizobia of varying effectiveness during optimal and insufficient water supplies. In our studies, we used symbiotic systems of soybean and rhizobia (Bradyrhizobium japonicum) that varied in efficiency and virulence. In the period of active nitrogen fixation by soybean, from the third-true-leaf stage until budding, we created different water-supply regimes for the plants, including optimal watering at the level of 60% of full field capacity (control) and insufficient, at the level of 30% (drought). When the soybean was flowering, we recovered the optimal level of water supply (resumed watering). In the studies, we employed microbiological, biochemical, and physiological approaches. We determined the specificity of how key enzymes of the phenol metabolism such as phenylalanine ammonia lyase, polyphenol oxidase and guaiacol peroxidase in the nodules, roots, and leaves of the soybean reacted to different levels of water supply, depending on the functional efficiency of the symbiotic system involving strains of B. japonicum, varying in effectiveness and virulence. In the effective soybean-rhizobium symbiosis, there occurred insignificant changes in the activity of phenol-metabolism enzymes in the nodules, roots, and leaves during drought and after action of the stress. This evidence is that in symbiosis with effective rhizobia B1-20, soybean could realize its own defensive systems that regulate optimal functioning of phenol metabolism in dehydration conditions. In the low-effective 107 and ineffective 604k symbiotic systems of soybean, there was observed unstable dynamics of the activity of enzymes in leaves and roots, manifested in intensification or inhibition of their activity levels during drought or post-stress period. This indicates malfunctioning of the processes associated with phenol metabolism in the soybean plants. We concluded that tolerance of legume-rhizobium symbiosis to water deprivation depends on mutual involvements of the both symbiotic partners – host plant and rhizobia, their ability to fully realize the defensive systems for activation of the key enzymatic complexes taking part in regulation of phenol metabolism in plants.

Asperphenalenones Isolated from the Biocontrol Agent Clonostachys rosea and Their Antimicrobial Activities.

Clonostachys rosea is a fungus widely distributed on Earth and has a high capacity to adapt to complex environments in soil, plants, or sea. It is an endophyte that can be used as a potential biocontrol agent to protect plants from pathogenic fungi, nematodes, and insects. However, the spectrum of secondary metabolites produced by C. rosea has only scarcely been studied. In the present study, eight new phenalenones, asperphenalenones F-M (1-8), together with two known derivatives, asperphenalenones E and B (9 and 10), were isolated from the axenic rice culture of this fungus. The structures of the new compounds were elucidated by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism, and gas chromatography-mass spectrometry analyses. Asperphenalenones J-M (5-8) are unusual phenalenone adducts that are conjugated to diterpenoid glycosides. Asperphenalenones F and H showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimal inhibitory concentrations of 12.5 and 25 μM, respectively. Asperphenalenone B exhibited low antiviral activity against the human immunodeficiency virus replication. Furthermore, asperphenalenones F and H exhibited low cytotoxicity against Jurkat cells, while all other compounds were devoid of cytotoxicity.

Fusarium proliferatum secondary metabolite profile in vitro depends on the origin of the isolates and is clearly reduced in stored garlic

Fusarium proliferatum as well as F. oxysporum are pathogens with a broad host range that includes garlic (Allium sativum). The losses of garlic due to these pathogens increased over the last years. Especially F. proliferatum was identified several times as the main cause of postharvest dry rot. This species is also known to produce mycotoxins, especially fumonisins. In this study, we aimed to identify and study the phylogeny of the Fusarium species diversity in garlic planting as well as stored material from two cultivars over two seasons. In addition, we surveyed the secondary metabolite production of the isolates obtained from this experimental design as well as in stored garlic intended for consumption. A total of 85 isolates were examined of which 84 % were identified as F. proliferatum. The distribution of the two species was similar for both seasons. In the phylogeny, no influence of season, planting material or stored garlic or cultivar could be detected. In contrast, an influence of the origin of the isolates on the broad spectrum of secondary metabolites could be demonstrated. The isolates showed strong production of fumonisins and other Fusarium metabolites in vitro. 25 % of the commercial garlic bulbs were contaminated with low levels of fumonisin, while 88 % were contaminated with moniliformin. Our results might indicate, that moniliformin plays a role in pathogenesis.

PHYTOCHEMISTRY AND PHARMACOLOGICAL BIO-ACTIVITIES OF LANNEA COROMANDELICA: A REVIEW

Lannea coromandelica is extensively employed as a medicinal herb across the globe. This research work focuses primarily on the phytochemistry, pharmaceutics, and bio-exertion of L. coromandelica. In ethnomedicine, several members of this species function as astringents, aiding in anti-oxidant, anti-inflammatory, and anti-diabetic and are helpful in other physiological functions. In addition, Lannea species’ therapeutic benefits were acknowledged in numerous scientific investigations. The conclusions derived from the current study corroborate that the therapeutic activities of L. coromandelica can be linked to the presence of a broad spectrum of secondary metabolites and bioactive phytocompounds such as phenols, flavonoids, tannins, and proteins, according to the current study. This review highlights phyto-assembly and phyto-activities such as a diuretic, cardiovascular, and bioactivities such as antiepileptic, antimicrobial, and anti-convulsant, and pharmaceutical activities such as anti-cancer, anti-diabetic, and anti-asthmatic properties.

Antimicrobial Activities of Secondary Metabolites from Model Mosses.

Plants synthetize a large spectrum of secondary metabolites with substantial structural and functional diversity, making them a rich reservoir of new biologically active compounds. Among different plant lineages, the evolutionarily ancient branch of non-vascular plants (Bryophytes) is of particular interest as these organisms produce many unique biologically active compounds with highly promising antibacterial properties. Here, we characterized antibacterial activity of metabolites produced by different ecotypes (strains) of the model mosses Physcomitrium patens and Sphagnum fallax. Ethanol and hexane moss extracts harbor moderate but unstable antibacterial activity, representing polar and non-polar intracellular moss metabolites, respectively. In contrast, high antibacterial activity that was relatively stable was detected in soluble exudate fractions of P. patens moss. Antibacterial activity levels in P. patens exudates significantly increased over four weeks of moss cultivation in liquid culture. Interestingly, secreted moss metabolites are only active against a number of Gram-positive, but not Gram-negative, bacteria. Size fractionation, thermostability and sensitivity to proteinase K assays indicated that the secreted bioactive compounds are relatively small (less than <10 kDa). Further analysis and molecular identification of antibacterial exudate components, combined with bioinformatic analysis of model moss genomes, will be instrumental in the identification of specific genes involved in the bioactive metabolite biosynthesis.

Anti-Quorum Sensing in Pathogenic Microbes Using Plant-Based Bioactive Phytochemicals

Infectious disease-causing pathogenic microorganisms grow rapidly within quorum sensing mediated biofilms. Attempts are made to restrict quorum sensing in pathogens, and the formation of biofilms has paved the way for the identification of bioactive phytochemicals. Anti-QS compounds have been proven to reduce bacterial pathogenicity in the past. Medicinal plants provide an enticing repertoire of phytochemicals with distinct microbial disease-controlling potential due to the vast spectrum of secondary metabolites included in extracts such as phenolics, quinones, flavonoids, alkaloids, terpenoids, and polyacetylenes. This review makes a specialty of the bioactive molecules produced using vegetation which have a target closer to quorum sensing accompanied via biofilm formation in pathogenic microbes.

Insights into in vitro phenotypic plasticity, growth and secondary metabolites of the mycobiont isolated from the lichen Platygramme caesiopruinosa.

The choice of inoculum for successful isolation and establishment of axenic lichen mycobiont culture is a key step towards eliminating endolichenic and lichenicolous fungi and other microbial contamination. The nutritional requirements of each lichen species are unique. This work reports on the isolation, phenotypic plasticity, growth and secondary metabolites from mycobiont culture of the pantropical lichen Platygramme caesiopruinosa. Media composition [Malt yeast extract (MY), Modified Murashige and Skoog (MMS) and Lilly and Barnett (LB) media] was optimized to determine nutritional requirements for optimal growth of this species as assessed by dry biomass and the occurrence of secondary metabolite. Furthermore, the role of different carbon sources in affecting growth, growth stages, phenotypic plasticity, biomass and spectrum of secondary metabolites produced of this mycobiont was examined. The molecular identity of the mycobiont culture was confirmed by amplifying mitochondrial small subunit (mtSSU) sequences. Cultures showed optimum biomass production in MYmediumwith 10% sucrose. The secondary metabolite profiles for each culture treatment were characterized using High-performance Thin-Layer Chromatography (HPTLC) and Gas Chromatography with Mass Spectrometric (GC-MS) analysis. The HPTLC spectral comparison, phenolic and iodine confirmatory analysis revealed the absence of phenolic metabolites and the presence of non-phenolic metabolites in mycobiont extracts, while GC-MS analysis revealed the biosynthesis of side chain fatty acids, hydrocarbons and sugar alcohol in mycobiont cultures treated with 10% supplemented sucrose as a carbon source.

Cynodon dactylon Pers.: A Review on Forage Crop and Medicinal Herb

Cynodon dactylon is a forage crop besides being a medicinal herb which has been holding a sacred position in our Indian culture. Its survival capacity in any ecological succession has forced it to exist as medicinal plant containing a broad spectrum of secondary metabolites like Cyanidin, Luteolin, apigenin having several therapeutic uses. The review paper has been designed in coordination with research articles to compile the various properties of the plant like its thriving capacity in tropical and subtropical regions where it can alter ecosystem by effecting nutrient cycles and community composition, diverse chemical composition, and therapeutic uses to name some such as diabetes, atherosclerosis etc., which could be used as an area of further research for mankind and environmental benefits.

Identification of Chemotypic Markers in Three Chemotype Categories of Cannabis Using Secondary Metabolites Profiled in Inflorescences, Leaves, Stem Bark, and Roots.

Previous chemotaxonomic studies of cannabis only focused on tetrahydrocannabinol (THC) dominant strains while excluded the cannabidiol (CBD) dominant strains and intermediate strains (THC ≈ CBD). This study investigated the utility of the full spectrum of secondary metabolites in different plant parts in three cannabis chemotypes (THC dominant, intermediate, and CBD dominant) for chemotaxonomic discrimination. Hierarchical clustering, principal component analysis (PCA), and canonical correlation analysis assigned 21 cannabis varieties into three chemotypes using the content and ratio of cannabinoids, terpenoids, flavonoids, sterols, and triterpenoids across inflorescences, leaves, stem bark, and roots. The same clustering results were obtained using secondary metabolites, omitting THC and CBD. Significant chemical differences were identified in these three chemotypes. Cannabinoids, terpenoids, flavonoids had differentiation power while sterols and triterpenoids had none. CBD dominant strains had higher amounts of total CBD, cannabidivarin (CBDV), cannabichromene (CBC), α-pinene, β-myrcene, (−)-guaiol, β-eudesmol, α-eudesmol, α-bisabolol, orientin, vitexin, and isovitexin, while THC dominant strains had higher total THC, total tetrahydrocannabivarin (THCV), total cannabigerol (CBG), camphene, limonene, ocimene, sabinene hydrate, terpinolene, linalool, fenchol, α-terpineol, β-caryophyllene, trans-β-farnesene, α-humulene, trans-nerolidol, quercetin, and kaempferol. Compound levels in intermediate strains were generally equal to or in between those in CBD dominant and THC dominant strains. Overall, with higher amounts of β-myrcene, (−)-guaiol, β-eudesmol, α-eudesmol, and α-bisabolol, intermediate strains more resemble CBD dominant strains than THC dominant strains. The results of this study provide a comprehensive profile of bioactive compounds in three chemotypes for medical purposes. The simultaneous presence of a predominant number of identified chemotype markers (with or without THC and CBD) could be used as chemical fingerprints for quality standardization or strain identification for research, clinical studies, and cannabis product manufacturing.

Somatic Embryogenesis in Centaurium erythraea Rafn-Current Status and Perspectives: A Review.

Centaurium erythraea (centaury) is a traditionally used medicinal plant, with a spectrum of secondary metabolites with confirmed healing properties. Centaury is an emerging model in plant developmental biology due to its vigorous regenerative potential and great developmental plasticity when cultured in vitro. Hereby, we review nearly two decades of research on somatic embryogenesis (SE) in centaury. During SE, somatic cells are induced by suitable culture conditions to express their totipotency, acquire embryogenic characteristics, and eventually give rise to somatic embryos. When SE is initiated from centaury root explants, the process occurs spontaneously (on hormone-free medium), directly (without the callusing phase), and the somatic embryos are of unicellular origin. SE from leaf explants has to be induced by plant growth regulators and is indirect (preceded by callusing). Histological observations and culture conditions are compared in these two systems. The changes in antioxidative enzymes were followed during SE from the leaf explants. Special focus is given to the role of arabinogalactan proteins during SE, which were analyzed using a variety of approaches. The newest and preliminary results, including centaury transcriptome, novel potential SE markers, and novel types of arabinogalactan proteins, are discussed as perspectives of centaury research.

Effect of Cannabis sativa L. root, leaf and inflorescence ethanol extracts on the chemotrophic response of entomopathogenic nematodes

Soils represent the natural habitat of entomopathogenic nematodes (EPNs). When moving in soil, EPNs are oriented to follow a chemical signal (chemotaxis). Cannabis sativa L. is known to secrete a very wide spectrum of secondary metabolites. Ethanol extracts (EE) of different C. sativa L. organs were used to study the effect on EPN chemotaxis. The root, leaf and inflorescence EE of two hemp varieties and two medical cannabis breeding lines were used in laboratory chemotaxis assays with three EPN species (Steinernema carpocapsae, S. feltiae and Heterorhabditis bacteriophora) at 20 and 25 °C. The content of terpenes and cannabinoids in C. sativa L. inflorescences was measured as well. Overall, EPNs were most attracted or repelled by inflorescence extracts, followed by leaves and roots. The most abundant terpene in hemp inflorescences was trans caryophyllene (38.2% on average), the highest contents of total cannabidiol, total cannabigerol and total tetrahydrocannabinol were 9.65%, 0.89% and 0.62%, respectively. The attraction effect of S. sativa L. EE is a highly interesting outcome and could lead to the development of attractant compounds in EPN biological control. Cannabinoids and terpenes may be responsible for pronounced effects on EPN chemotaxis.

Elaborated regulation of griseofulvin biosynthesis in Penicillium griseofulvum and its role on conidiation and virulence

Penicilium griseofulvum, the causal agent of apple blue mold, is able to produce in vitro and on apple a broad spectrum of secondary metabolites (SM), including patulin, roquefortine C and griseofulvin. Among them, griseofulvin is known for its antifungal and antiproliferative activity, and has received interest in many sectors, from medicine to agriculture. The biosynthesis of SM is finely regulated by filamentous fungi and can involve global regulators and pathway specific regulators, which are usually encoded by genes present in the same gene cluster as the backbone gene and tailoring enzymes. In the griseofulvin gene cluster, two putative transcription factors were previously identified, encoded by genes gsfR1 and gsfR2, and their role has been investigated in the present work. Analysis of P. griseofulvum knockout mutants lacking either gene suggest that gsfR2 forms part of a different pathway and gsfR1 exhibits many spectra of action, acting as regulator of griseofulvin and patulin biosynthesis and influencing conidia production and virulence on apple. The analysis of gsfR1 promoter revealed that the regulation of griseofulvin biosynthesis is also controlled by global regulators in response to many environmental stimuli, such as carbon and nitrogen. The influence of carbon and nitrogen on griseofulvin production was further investigated and verified, revealing a complex network of response and confirming the central role of gsfR1 in many processes in P. griseofulvum.

Biocidal effects of volatile organic compounds produced by the myxobacterium Corrallococcus sp. EGB against fungal phytopathogens

Myxobacteria have excellent biocontrol activity against various phytopathogens due to their rich spectrum of secondary metabolites and active predatory characteristics. In this study, the mycelial growth of Fusarium oxysporum f. sp. cucumerinum (FOC) was found to be significantly inhibited by volatile compounds (VOCs) produced by Corallococcus sp. EGB. A total of 32 compounds were identified among the VOCs produced by strain EGB, of which isooctanol exhibited the highest antifungal activity, with dosages of 3.75 and 4.0 μL/plate being sufficient to suppress FOC and Penicillum digitatum, respectively. Isooctanol was found to damage the cell wall and cell membranes of FOC and P. digitatum. Apoptosis-like cell death of FOC and P. digitatum induced by isooctanol was observed subsequently due to the accumulation of reactive oxygen species (ROS). The transcription level of genes related to cell wall integrity (CWI) pathway and redox reactions were significantly upregulated by 15- to 40-fold, indicating the stress caused by isooctanol. Postharvest storage experiments showed that the disease severity of post-harvest oranges infected with P. digitatum could be significantly reduced by isooctanol at 114.2 μL/L.

Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots for Medicinal Purposes

Cannabis research has historically focused on the most prevalent cannabinoids. However, extracts with a broad spectrum of secondary metabolites may have increased efficacy and decreased adverse effects compared to cannabinoids in isolation. Cannabis’s complexity contributes to the length and breadth of its historical usage, including the individual application of the leaves, stem barks, and roots, for which modern research has not fully developed its therapeutic potential. This study is the first attempt to profile secondary metabolites groups in individual plant parts comprehensively. We profiled 14 cannabinoids, 47 terpenoids (29 monoterpenoids, 15 sesquiterpenoids, and 3 triterpenoids), 3 sterols, and 7 flavonoids in cannabis flowers, leaves, stem barks, and roots in three chemovars available. Cannabis inflorescence was characterized by cannabinoids (15.77–20.37%), terpenoids (1.28–2.14%), and flavonoids (0.07–0.14%); the leaf by cannabinoids (1.10–2.10%), terpenoids (0.13–0.28%), and flavonoids (0.34–0.44%); stem barks by sterols (0.07–0.08%) and triterpenoids (0.05–0.15%); roots by sterols (0.06–0.09%) and triterpenoids (0.13–0.24%). This comprehensive profile of bioactive compounds can form a baseline of reference values useful for research and clinical studies to understand the “entourage effect” of cannabis as a whole, and also to rediscover therapeutic potential for each part of cannabis from their traditional use by applying modern scientific methodologies.

Hypericum spp.: An Update on the Biological Activities and Metabolic Profiles.

Plants from the genus Hypericum, one genus of the Hypericaceae family, have attracted a lot of attention for their potential pharmaceutical applications. Most of the studies in the literature focus on H. perforatum L. (common St. John's wort), whose complex spectrum of bioactive compounds makes this species one of the top herbal remedies and supplements in the world. It is also important to compare the studies on other Hypericum species, both from the phytochemical and biological point of view. The aim of this review was to provide an update of most recent studies about biological investigations of plants belonging to Hypericum genus. The metabolic profiles of Hypericum spp. were also discussed in order to present a spectrum of secondary metabolites not previously identified in this genus.

Endophytic Fungi of Native Salvia abrotanoides Plants Reveal High Taxonomic Diversity and Unique Profiles of Secondary Metabolites.

Endophytic fungi are often embedded in their host’s metabolic networks, which can result in alterations of metabolite production and higher amounts of active compounds in medicinal plants. This study reports the occurrence, diversity, and secondary metabolite profiles of endophytic fungi isolated from Salvia abrotanoides plants obtained from three geographically distinct sites in Iran. A total of 56 endophytic fungi were isolated from roots and leaves of S. abrotanoides; site-specificity and root-dominated colonization was found to be a general characteristic of the endophytes. Based on molecular identification, the endophytic fungi were classified into 15 genera. Mycelial extracts of these isolates were subjected to high-resolution mass spectrometry analyses and revealed a broad spectrum of secondary metabolites. Our results demonstrated that Penicillium canescens, P. murcianum, Paraphoma radicina, and Coniolariella hispanica are producers of cryptotanshinone, which is a main bioactive compound of S. abrotanoides. Moreover, it was shown that it can be produced independent of the host plant. The effect of exogenous gibberellin on S. abrotanoides and endophytic fungi was shown to have a positive effect on increasing the cryptotanshinone production in the plant as well as in endophytic fungi cultivated under axenic conditions. Our findings provide further evidence that endophytic fungi play an important role in the production plant bioactive metabolites. Moreover, they provide an exploitable basis to increase cryptotanshinone production in S. abrotanoides.

A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte Pestalotiopsis microspora, a Taxol Producer.

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in gα1Δ, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.

Curvulin and Phaeosphaeride A from Paraphoma sp. VIZR 1.46 Isolated from Cirsium arvense as Potential Herbicides.

Phoma-like fungi are known as producers of diverse spectrum of secondary metabolites, including phytotoxins. Our bioassays had shown that extracts of Paraphoma sp. VIZR 1.46, a pathogen of Cirsium arvense, are phytotoxic. In this study, two phytotoxically active metabolites were isolated from Paraphoma sp. VIZR 1.46 liquid and solid cultures and identified as curvulin and phaeosphaeride A, respectively. The latter is reported also for the first time as a fungal phytotoxic product with potential herbicidal activity. Both metabolites were assayed for phytotoxic, antimicrobial and zootoxic activities. Curvulin and phaeosphaeride A were tested on weedy and agrarian plants, fungi, Gram-positive and Gram-negative bacteria, and on paramecia. Curvulin was shown to be weakly phytotoxic, while phaeosphaeride A caused severe necrotic lesions on all the tested plants. To evaluate phaeosphaeride A’s herbicidal efficacy, the phytotoxic activity of this compound in combination with five different adjuvants was studied. Hasten at 0.1% (v/v) was found to be the most potent and compatible adjuvant, and its combination with 0.5% (v/v) semi-purified extract of Paraphoma sp. VIZR 1.46 solid culture exhibited maximum damage to C. arvense plants. These findings may offer significant importance for further investigation of herbicidal potential of phaeosphaeride A and possibly in devising new herbicide of natural origin.