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Biological Research Jul 2019In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological... (Review)
Review
In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological processes, and recent increasing evidences have implicated stress and defense response signaling in their production. The type and concentration(s) of secondary molecule(s) produced by a plant are determined by the species, genotype, physiology, developmental stage and environmental factors during growth. This suggests the physiological adaptive responses employed by various plant taxonomic groups in coping with the stress and defensive stimuli. The past recent decades had witnessed renewed interest to study abiotic factors that influence secondary metabolism during in vitro and in vivo growth of plants. Application of molecular biology tools and techniques are facilitating understanding the signaling processes and pathways involved in the SMs production at subcellular, cellular, organ and whole plant systems during in vivo and in vitro growth, with application in metabolic engineering of biosynthetic pathways intermediates.
Topics: Cell Culture Techniques; Gene Expression Regulation, Plant; Plant Growth Regulators; Plant Physiological Phenomena; Plant Roots; Plant Shoots; Plants; Secondary Metabolism; Signal Transduction; Stress, Physiological
PubMed: 31358053
DOI: 10.1186/s40659-019-0246-3 -
Biotechnology Advances Nov 2015Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for... (Review)
Review
Genomic sequence data have revealed the presence of a large fraction of putatively silent biosynthetic gene clusters in the genomes of actinomycetes that encode for secondary metabolites, which are not detected under standard fermentation conditions. This review focuses on the effects of biological (co-cultivation), chemical, as well as molecular elicitation on secondary metabolism in actinomycetes. Our review covers the literature until June 2014 and exemplifies the diversity of natural products that have been recovered by such approaches from the phylum Actinobacteria.
Topics: Actinobacteria; Biological Products; Coculture Techniques; Multigene Family; Secondary Metabolism
PubMed: 26087412
DOI: 10.1016/j.biotechadv.2015.06.003 -
Molecules (Basel, Switzerland) Jul 2021The islands of the South Pacific Ocean have been in the limelight for natural product biodiscovery, due to their unique and pristine tropical waters and environment. The... (Review)
Review
The islands of the South Pacific Ocean have been in the limelight for natural product biodiscovery, due to their unique and pristine tropical waters and environment. The Kingdom of Tonga is an archipelago in the central Indo-Pacific Ocean, consisting of 176 islands, 36 of which are inhabited, flourishing with a rich diversity of flora and fauna. Many unique natural products with interesting bioactivities have been reported from Indo-Pacific marine sponges and other invertebrate phyla; however, there have not been any reviews published to date specifically regarding natural products from Tongan marine organisms. This review covers both known and new/novel Marine Natural Products (MNPs) and their biological activities reported from organisms collected within Tongan territorial waters up to December 2020, and includes 109 MNPs in total, the majority from the phylum Porifera. The significant biological activity of these metabolites was dominated by cytotoxicity and, by reviewing these natural products, it is apparent that the bulk of the new and interesting biologically active compounds were from organisms collected from one particular island, emphasizing the geographic variability in the chemistry between these organisms collected at different locations.
Topics: Animals; Aquatic Organisms; Biodiversity; Biological Products; Drug Discovery; Pacific Ocean; Porifera; Secondary Metabolism; Tonga; Tropical Climate
PubMed: 34361690
DOI: 10.3390/molecules26154534 -
PloS One 2022Bacteria employ secondary metabolism to combat competitors, and xenobiotic metabolism to survive their chemical environment. This project has aimed to introduce a...
Bacteria employ secondary metabolism to combat competitors, and xenobiotic metabolism to survive their chemical environment. This project has aimed to introduce a bacterial collection enabling comprehensive comparative investigations of those functions. The collection comprises 120 strains (Proteobacteria, Actinobacteria and Firmicutes), and was compiled on the basis of the broad taxonomic range of isolates and their postulated biosynthetic and/or xenobiotic detoxification capabilities. The utility of the collection was demonstrated in two ways: first, by performing 5144 co-cultures, recording inhibition between isolates and employing bioinformatics to predict biosynthetic gene clusters in sequenced genomes of species; second, by screening for xenobiotic sensitivity of isolates against 2-benzoxazolinone and 2-aminophenol. The co-culture medium of Bacillus siamensis D9 and Lysinibacillus sphaericus DSM 28T was further analysed for possible antimicrobial compounds, using liquid chromatography-mass spectrometry (LC-MS), and guided by computational predictions and the literature. Finally, LC-MS analysis demonstrated N-acetylation of 3,4-dichloroaniline (a toxic pesticide residue of concern) by the actinobacterium Tsukamurella paurometabola DSM 20162T which is highly tolerant of the xenobiotic. Microbial collections enable "pipeline" comparative screening of strains: on the one hand, bacterial co-culture is a promising approach for antibiotic discovery; on the other hand, bioremediation is effective in combating pollution, but requires knowledge of microbial xenobiotic metabolism. The presented outcomes are anticipated to pave the way for studies that may identify bacterial strains and/or metabolites of merit in biotechnological applications.
Topics: Bacteria; Firmicutes; Proteobacteria; Secondary Metabolism; Xenobiotics
PubMed: 35834592
DOI: 10.1371/journal.pone.0271125 -
MSphere Apr 2020Fungi are rich sources of secondary metabolites of pharmaceutical importance, such as antibiotics, antitumor agents, and immunosuppressants, as well as of harmful...
Fungi are rich sources of secondary metabolites of pharmaceutical importance, such as antibiotics, antitumor agents, and immunosuppressants, as well as of harmful toxins. Secondary metabolites play important roles in the development and pathogenesis of fungi. LaeA is a global regulator of secondary metabolism and was originally reported in ; however, its role in secondary metabolism in has not yet been reported. Here, we investigated the role of a gene homologous to (loss of expression) of spp. in , named (). Studies on overexpression and knockdown strains have suggested that this gene acts as a negative regulator of sporulation and melanin synthesis. However, it is not involved in the growth and pathogenesis of Transcriptomic data indicated that regulated genes involved in secondary metabolism. Interestingly, we observed (for the first time, to our knowledge) that this gene is involved in benzylpenicillin (penicillin G) synthesis in Overexpression of increased penicillin G production, whereas the silenced strain showed a complete absence of penicillin G compared to its presence in the wild type. We also observed that LaeA interacted with VeA, a velvet family protein involved in fungal development and secondary metabolism, in the nucleus. This study showed that though may not make any contribution in rice blast fungal pathogenesis, it regulates secondary metabolism in and thus can be further studied for identifying other new uncharacterized metabolites in this fungus. causes blast disease, the most serious disease of cultivated rice affecting global rice production. The genome of has been shown to have a number of genes involved in secondary metabolism, but most of them are uncharacterized. In fact, compared to studies of other filamentous fungi, hardly any work has been done on secondary metabolism in It is shown here (for the first time, to our knowledge) that penicillin G is being synthesized in and that is involved in this process. This is the first step in understanding the penicillin G biosynthesis pathway in This study also unraveled the details of how LaeA works by forming a nuclear complex with VeA in , thus indicating functional conservation of such a gene across filamentous fungi. All these findings open up avenues for more relevant investigations on the genetic regulation of secondary metabolism in .
Topics: Ascomycota; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Genes, Regulator; Oryza; Plant Diseases; Secondary Metabolism
PubMed: 32238572
DOI: 10.1128/mSphere.00936-19 -
International Journal of Molecular... Nov 2020Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly... (Review)
Review
Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Moreover, the relationship between pathogenicity and secondary metabolites remains unclear. To activate silent gene clusters in fungi, successful approaches such as epigenetic control, promoter exchange, and heterologous expression have been reported. , a well-characterized plant pathogenic fungus, is the causal pathogen of rice blast disease. is also rich in secondary metabolism genes. However, biosynthetic genes for only four groups of secondary metabolites have been well characterized in this fungus. Biosynthetic genes for two of the four groups of secondary metabolites have been identified by activating secondary metabolism. This review focuses on the biosynthesis and roles of the four groups of secondary metabolites produced by . These secondary metabolites include melanin, a polyketide compound required for rice infection; pyriculols, phytotoxic polyketide compounds; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi including endophytes and plant pathogens; and tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique NRPS-PKS enzyme.
Topics: Ascomycota; Gene Expression Regulation, Fungal; Oryza; Plant Diseases; Secondary Metabolism
PubMed: 33218033
DOI: 10.3390/ijms21228698 -
Toxins Apr 2022Chromatin structure is a major regulator of DNA-associated processes, such as transcription, DNA repair, and replication. Histone post-translational modifications, or... (Review)
Review
Chromatin structure is a major regulator of DNA-associated processes, such as transcription, DNA repair, and replication. Histone post-translational modifications, or PTMs, play a key role on chromatin dynamics. PTMs are involved in a wide range of biological processes in eukaryotes, including fungal species. Their deposition/removal and their underlying functions have been extensively investigated in yeasts but much less in other fungi. Nonetheless, the major role of histone PTMs in regulating primary and secondary metabolisms of filamentous fungi, including human and plant pathogens, has been pinpointed. In this review, an overview of major identified PTMs and their respective functions in fungi is provided, with a focus on filamentous fungi when knowledge is available. To date, most of these studies investigated histone acetylations and methylations, but the development of new methodologies and technologies increasingly allows the wider exploration of other PTMs, such as phosphorylation, ubiquitylation, sumoylation, and acylation. Considering the increasing number of known PTMs and the full range of their possible interactions, investigations of the subsequent Histone Code, i.e., the biological consequence of the combinatorial language of all histone PTMs, from a functional point of view, are exponentially complex. Better knowledge about histone PTMs would make it possible to efficiently fight plant or human contamination, avoid the production of toxic secondary metabolites, or optimize the industrial biosynthesis of certain beneficial compounds.
Topics: Chromatin; DNA; Histones; Humans; Protein Processing, Post-Translational; Secondary Metabolism
PubMed: 35622565
DOI: 10.3390/toxins14050317 -
Molecules (Basel, Switzerland) Apr 2015Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants.... (Review)
Review
Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field.
Topics: Animals; Biological Evolution; Ecosystem; Humans; Longevity; Phytochemicals; Secondary Metabolism
PubMed: 25871373
DOI: 10.3390/molecules20046544 -
Scientific Reports Feb 2023The filamentous fungus Trichoderma reesei is a prolific producer of plant cell wall degrading enzymes, which are regulated in response to diverse environmental signals...
The filamentous fungus Trichoderma reesei is a prolific producer of plant cell wall degrading enzymes, which are regulated in response to diverse environmental signals for optimal adaptation, but also produces a wide array of secondary metabolites. Available carbon source and light are the strongest cues currently known to impact secreted enzyme levels and an interplay with regulation of secondary metabolism became increasingly obvious in recent years. While cellulase regulation is already known to be modulated by different mitogen activated protein kinase (MAPK) pathways, the relevance of the light signal, which is transmitted by this pathway in other fungi as well, is still unknown in T. reesei as are interconnections to secondary metabolism and chemical communication under mating conditions. Here we show that MAPkinases differentially influence cellulase regulation in light and darkness and that the Hog1 homologue TMK3, but not TMK1 or TMK2 are required for the chemotropic response to glucose in T. reesei. Additionally, MAPkinases regulate production of specific secondary metabolites including trichodimerol and bisorbibutenolid, a bioactive compound with cytostatic effect on cancer cells and deterrent effect on larvae, under conditions facilitating mating, which reflects a defect in chemical communication. Strains lacking either of the MAPkinases become female sterile, indicating the conservation of the role of MAPkinases in sexual fertility also in T. reesei. In summary, our findings substantiate the previously detected interconnection of cellulase regulation with regulation of secondary metabolism as well as the involvement of MAPkinases in light dependent gene regulation of cellulase and secondary metabolite genes in fungi.
Topics: Cellulase; Secondary Metabolism; Trichoderma; Sexual Development; Gene Expression Regulation, Fungal; Fungal Proteins
PubMed: 36732590
DOI: 10.1038/s41598-023-28938-w -
PLoS Computational Biology Aug 2023In microorganisms, different from primary metabolism for cellular growth, secondary metabolism is for ecological interactions and stress responses and an important... (Review)
Review
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.
Topics: Secondary Metabolism; Cell Cycle; Cell Proliferation; Computational Biology; Engineering
PubMed: 37619239
DOI: 10.1371/journal.pcbi.1011391