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Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature (Tg) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.
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Carbohydrates, which are a vital dietary component, undergo digestion and gut fermentation through microbial enzymes to produce beneficial short-chain fatty acids. Certain carbohydrates selectively modulate the gut microbiota, impacting host health. Carbohydrate-active enzymes within the gut microbiota significantly contribute to carbohydrate utilization and microbial diversity. Despite their importance, the structural complexity of carbohydrates poses analytical challenges. However, recent advancements, notably, mass spectrometry, have allowed for their characterization and functional analysis. This review examines the intricate relationship between dietary carbohydrates and the gut microbiota, highlighting the crucial role of advanced analytical techniques in understanding their diversity and implications. These advancements provide valuable insights into carbohydrate bioactivity. Integrating high-throughput analysis with next-generation sequencing provides deeper insights into gut microbial interactions, potentially revealing which carbohydrate structures are beneficial for gut health.
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Structure, stability, electronic structure, spectroscopy and chemical bonding properties of a fluorine atom doped gas-phase small to medium-sized magnesium clusters, FMgn (n = 2-20), systematically investigated by CALYPSO software together with density functional theory (DFT). Structural calculations showed that FMgn has a structural diversity which is rarely reported in other magnesium-based clusters before. F atoms were always located in the outer layer of the Mgn host clusters and only two or three Mg atoms surround it. FMg18 was revealed to be supposed to have robust relative stability. Charge transfer and density of states were calculated for analyzing the electronic structure characteristics. Theoretical calculations of IR, Raman and UV-Vis spectra were computed to provide data guidelines for future experimental observations. Finally, the F-Mg and Mg-Mg chemical bonds of the FMgn clusters were analyzed, including the critical bonding points (BCPs) of Laplacian of electron density (Δρ), electron localization function (ELF) and interaction region indicator (IRI). The kind and strength of chemical bonds reveal the mechanism by which the F atom was rapidly stabilized by Mgn (n = 2-20) host clusters.
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The realm of titanium coordination polymer research is still in its nascent stages and presents a formidable challenge in the field of coordination chemistry. In recent decades, the focus has predominantly been on manipulating titanium reactions in solution, resulting in the synthesis of ≈60 targeted compounds. Despite the limited number of documented instances, these materials showcase a diverse array of structures, encompassing 1D chains, 2D layers, and 3D frameworks. This suggests potential for fine-tuning coordination modes and structural features in future investigations. Moreover, titanium coordination polymers not only exhibit photo-active and photo-responsive properties but also hold promise for various other significant applications. This article offers an exhaustive review tracing the evolution of titanium coordination polymer development while providing an update on recent advancements. The review encompasses a synopsis of reported synthetic strategies, methodologies, structural diversity, and associated applications. Additionally, it delves into critical issues that necessitate attention for future progressions and proposes potential avenues to effectively propel this research field forward at an accelerated pace.
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Vegetation regulates microclimate stability through biophysical mechanisms such as evaporation, transpiration and shading. Therefore, thermal conditions in tree-dominated habitats will frequently differ significantly from standardized free-air temperature measurements. The ability of forests to buffer temperatures nominates them as potential sanctuaries for tree species intolerant to the increasingly challenging thermal conditions established by climate change. Although many factors influencing thermal conditions beneath the vegetation cover have been ascertained, the role of three-dimensional vegetation structure in regulating the understory microclimate remains understudied. Recent advances in remote sensing technologies, such as terrestrial laser scanning, have allowed scientists to capture the three-dimensional structural heterogeneity of vegetation with a high level of accuracy. Here, we examined the relationships between vegetation structure parametrized from voxelized laser scanning point clouds, air and soil temperature ranges, as well as offsets between field-measured temperatures and gridded free-air temperature estimates in 17 sites in a tropical mountain ecosystem in Southeast Kenya. Structural diversity generally exerted a cooling effect on understory temperatures, but vertical diversity and stratification explained more variation in the understory air and soil temperature ranges (30%-40%) than canopy cover (27%), plant area index (24%) and average stand height (23%). We also observed that the combined effects of stratification, canopy cover and elevation explained more than half of the variation (53%) in understory air temperature ranges. Stratification's attenuating effect was consistent across different levels of elevation. Temperature offsets between field measurements and free-air estimates were predominantly controlled by elevation, but stratification and structural diversity were influential predictors of maximum and median temperature offsets. Moreover, stable understory temperatures were strongly associated with a large offset in daytime maximum temperatures, suggesting that structural diversity primarily contributes to thermal stability by cooling daytime maximum temperatures. Our findings shed light on the thermal influence of vertical vegetation structure and, in the context of tropical land-use change, suggest that decision-makers aiming to mitigate the thermal impacts of land conversion should prioritize management practices that preserve structural diversity by retaining uneven-aged trees and mixing plant species of varying sizes, e.g., silvopastoral, or agroforestry systems.
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Mudança Climática , Ecossistema , Microclima , Clima Tropical , Árvores , Humanos , Temperatura , Florestas , Biodiversidade , QuêniaRESUMO
The escalating crisis of antimicrobial resistance (AMR) underscores the urgent need for novel antimicrobials. One promising strategy is the exploration of structural diversity, as diverse structures can lead to diverse biological activities and mechanisms of action. This review delves into the role of structural diversity in antimicrobial discovery, highlighting its influence on factors such as target selectivity, binding affinity, pharmacokinetic properties, and the ability to overcome resistance mechanisms. We discuss various approaches for exploring structural diversity, including combinatorial chemistry, diversity-oriented synthesis, and natural product screening, and provide an overview of the common mechanisms of action of antimicrobials. We also describe techniques for investigating these mechanisms, such as genomics, proteomics, and structural biology. Despite significant progress, several challenges remain, including the synthesis of diverse compound libraries, the identification of active compounds, the elucidation of complex mechanisms of action, the emergence of AMR, and the translation of laboratory discoveries to clinical applications. However, emerging trends and technologies, such as artificial intelligence, high-throughput screening, next-generation sequencing, and open-source drug discovery, offer new avenues to overcome these challenges. Looking ahead, we envisage an exciting future for structural diversity-oriented antimicrobial discovery, with opportunities for expanding the chemical space, harnessing the power of nature, deepening our understanding of mechanisms of action, and moving toward personalized medicine and collaborative drug discovery. As we face the continued challenge of AMR, the exploration of structural diversity will be crucial in our search for new and effective antimicrobials.
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Descoberta de Drogas , Descoberta de Drogas/métodos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Ensaios de Triagem em Larga EscalaRESUMO
Prenylation plays a pivotal role in the diversification and biological activities of natural products. This study presents the functional characterization of TolF, a multiple prenyltransferase from Tolypocladium inflatum. The heterologous expression of tolF in Aspergillus oryzae, coupled with feeding the transformed strain with paxilline, resulted in the production of 20- and 22-prenylpaxilline. Additionally, TolF demonstrated the ability to prenylated the reduced form of paxilline, ß-paxitriol. A related prenyltransferase TerF from Chaunopycnis alba, exhibited similar substrate tolerance and regioselectivity. In vitro enzyme assays using purified recombinant enzymes TolF and TerF confirmed their capacity to catalyze prenylation of paxilline, ß-paxitriol, and terpendole I. Based on previous reports, terpendole I should be considered a native substrate. This work not only enhances our understanding of the molecular basis and product diversity of prenylation reactions in indole diterpene biosynthesis, but also provides insights into the potential of fungal indole diterpene prenyltransferase to alter their position specificities for prenylation. This could be applicable for the synthesis of industrially useful compounds, including bioactive compounds, thereby opening up new avenues for the development of novel biosynthetic strategies and pharmaceuticals. KEY POINTS: ⢠The study characterizes TolF as a multiple prenyltransferase from Tolypocladium inflatum. ⢠TerF from Chaunopycnis alba shows similar substrate tolerance and regioselectivity compared to TolF. ⢠The research offers insights into the potential applications of fungal indole diterpene prenyltransferases.
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Dimetilaliltranstransferase , Diterpenos , Hypocreales , Dimetilaliltranstransferase/metabolismo , Prenilação , Indóis/metabolismo , Diterpenos/metabolismo , Especificidade por SubstratoRESUMO
Growing demand for the tasty and healthy food has driven the development of low-calorie sweeteners, sweet taste modulators, and bitter masking compounds originated from natural sources. With the discovery of human taste receptors, increasing numbers of sweet taste modulators have been identified through human taste response and molecular docking techniques. However, the discovery of novel taste-active molecules in nature can be accelerated by using advanced spectrometry technologies based on structure-activity relationships (SARs). SARs explain why structurally similar compounds can elicit similar taste qualities. Given the characterization of structural information from reported data, strategies employing SAR techniques to find structurally similar compounds become an innovative approach to expand knowledge of sweeteners. This review aims to summarize the structural patterns of known natural non-nutritive sweeteners, sweet taste enhancers, and bitter masking compounds. Innovative SAR-based approaches to explore sweetener derivatives are also discussed. Most sweet-tasting flavonoids belong to either the flavanonols or the dihydrochalcones and known bitter masking molecules are flavanones. Based on SAR findings that structural similarities are related to the sensory properties, innovative methodologies described in this paper can be applied to screen and discover the derivatives of taste-active compounds or potential taste modulators.
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Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.
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Food security is an important issue in the 21st century; preventing and controlling crop diseases and pests are the key to solve this problem. The creation of new pesticides based on natural products is an important and effective method. Herein, coumarins were selected as parent structures, and a series of their derivatives were designed, synthesized, and evaluated for their antiviral activities, fungicidal activities, and insecticidal activities. We found that coumarin derivatives exhibited good to excellent antiviral activities against tobacco mosaic virus (TMV). The antiviral activities of I-1, I-2a, I-4b, II-2c, II-2g, II-3, and II-3b are better than that of ribavirin at 500 µg/mL. Molecular docking research showed that these compounds had a strong interaction with TMV CP. These compounds also showed broad-spectrum fungicidal activities against 14 plant pathogenic fungi. The EC50 values of I-1, I-2a, I-3c, and II-2d are in the range of 1.56-8.65 µg/mL against Rhizoctonia cerealis, Physalospora piricola, Sclerotinia sclerotiorum, and Pyricularia grisea. Most of the compounds also displayed good insecticidal activities against Mythimna separata. Pesticide-likeness analysis showed that these compounds are following pesticide-likeness and have the potential to be developed as pesticide candidates. The present work lays a foundation for the discovery of novel pesticide lead compounds based on coumarin derivatives.
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Fungicidas Industriais , Inseticidas , Praguicidas , Vírus do Mosaico do Tabaco , Relação Estrutura-Atividade , Praguicidas/farmacologia , Fungicidas Industriais/química , Antivirais/química , Cumarínicos/química , Simulação de Acoplamento Molecular , Inseticidas/química , Desenho de FármacosRESUMO
Dibenzofurans are a small class of natural products with versatile biological activities that used to be thought to come mainly from lichens and ascomycetes. In fact, they are also distributed widely in higher plants, especially in the families Rosaceae and Myrtaceae. Dibenzofurans and derivatives from lichens and ascomycetes have been well reviewed, but dibenzofurans from all biological sources in nature have not been reviewed. In this review, dibenzofurans from all natural sources have been comprehensively reviewed, and a total of 211 dibenzofurans isolated and identified from organisms between 1843 and March 2023 are categorized and discussed, including their biosynthesis, structural diversity, sources, and bioactivities.
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Ascomicetos , Líquens , Humanos , Dibenzofuranos , Líquens/químicaRESUMO
The Keap1-Nrf2-ARE signaling pathway is an attractive therapeutic target for the prevention and treatment of oxidative stress-associated diseases by activating the cellular expression of cytoprotective enzymes and proteins. Small molecule inhibitors can directly disrupt the Keap1-Nrf2 protein-protein interaction (PPI), resulting in elevated levels of Nrf2 protein and subsequent stimulation of related antioxidant responses. Previously, we found that 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N'-diacetic acid derivatives with an ether type C2-substituent on the benzene or naphthalene core exhibited potent inhibitory activities with IC50's in the submicromolar or nanomolar range. We here describe a more detailed structure-activity relationship study around the C2 substituents containing various polar linkers shedding new insight on their binding interactions with the Keap1 Kelch domain. The key observation from our findings is that the substituents at the C2-position of the benzene or naphthalene scaffold impact their inhibitory potencies in biochemical assays as well as activities in cell culture. The biochemical FP and TR-FRET assays revealed that the naphthalene derivatives 17b and 18 with an additional carboxylate at the C2 were the most active inhibitors against Keap1-Nrf2 PPI. In the cell-based assay, the two compounds were shown to be potent Nrf2 activators of the transcription of the Nrf2-dependent genes, such as HMOX2, GSTM3, and NQO1.
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Benzeno , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Naftalenos/farmacologia , Naftalenos/química , Ligação ProteicaRESUMO
Heterologous biosynthesis has become an effective means to activate fungal silent biosynthetic gene clusters (BGCs) and efficiently utilize fungal genetic resources. Herein, thirteen labdane diterpene derivatives, including five undescribed ones named talarobicins A-E (3-7), were discovered via heterologous expression of a silent BGC (labd) in Aspergillus nidulans. Their structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as electronic circular dichroism (ECD) calculations. These labdanes belong to four skeleton types, and talarobicin B (4) is the first 3,18-dinor-2,3:4,18-diseco-labdane diterpene with the cleavage of the C2-C3 bond in ring A and the decarboxylation at C-3 and C-18. Talarobicin B (4) represents the key intermediate in the biosynthesis of penioxalicin and compound 13. The combinatorial heterologous expression and feeding experiments revealed that the cytochrome P450 enzymes LabdC, LabdE, and LabdF were responsible for catalyzing various chemical reactions, such as oxidation, decarboxylation, and methylation. All of the compounds are noncytotoxic, and compounds 2 and 8 displayed inhibitory effects against methicillin-resistant coagulase-negative staphylococci (MRCNS) and Bacillus cereus.
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Aspergillus nidulans , Diterpenos , Talaromyces , Talaromyces/metabolismo , Diterpenos/química , Sistema Enzimático do Citocromo P-450 , Espectroscopia de Ressonância Magnética , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Estrutura MolecularRESUMO
α-Amylase is a generally acknowledged molecular target of a distinct class of antidiabetic drugs named α-glucosidase inhibitors. This class of medications is scarce and rather underutilized, and treatment with current commercial drugs is accompanied by unpleasant adverse effects. However, mammalian α-amylase inhibitors are abundant in nature and form an extensive pool of high-affinity ligands that are available for drug discovery. Individual compounds and natural extracts and preparations are promising therapeutic agents for conditions associated with impaired starch metabolism, e.g., diabetes mellitus, obesity, and other metabolic disorders. This review focuses on the structural diversity and action mechanisms of active natural products with inhibitory activity toward mammalian α-amylases, and emphasizes proteinaceous inhibitors as more effective compounds with significant potential for clinical use.
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Doenças Metabólicas , alfa-Amilases , Animais , Humanos , alfa-Amilases/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Inibidores de Glicosídeo Hidrolases/química , Doenças Metabólicas/tratamento farmacológico , alfa-Glucosidases/química , Extratos Vegetais/uso terapêutico , Mamíferos/metabolismoRESUMO
Paper mulberry (Broussonetia papyrifera) is currently an invasive species on several continents. However, little is known about whether paper mulberry has a competitive advantage over its surrounding trees in its native distribution range, subtropical regions of China. Here, we determined the relative intraspecific and interspecific competitive capacity of paper mulberry in three subtropical deciduous broad-leaved forests using the indices of structural diversity including the mixing index, the tree-tree interval index, and the diameter/height differentiation index. It was found that more than 80% of mingling index values were not greater than 0.25, suggesting a stronger competitiveness of paper mulberry relative to other tree species. The tree-tree interval index values ranged between 1 m and 2 m, suggesting a strong competition between paper mulberry and its neighbors. Moreover, more than 60% of the height differentiation index and diameter differentiation index values were positive, suggesting that the reference paper mulberry had a slight competitive advantage over neighboring trees in both the horizontal and vertical planes. These collectively suggest a competitive advantage over other tree species in the native distribution range, which may play a significant role in the ecological invasion of paper mulberry. Our findings not only help to reveal the invasion mechanism of paper mulberry, but also provide an important reference for the management and utilization of paper mulberry in invaded areas.
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Sansanmycins represent a family of uridyl peptide antibiotics with antimicrobial activity specifically against Mycobacterium tuberculosis (including drug-resistant M. tuberculosis) and Pseudomonas aeruginosa. They target translocase I (MraY) to inhibit bacterial cell wall assembly. Given the unique mechanism of action, sansanmycin has emerged as a potential lead compound for developing new anti-tuberculosis drugs, while the 5'-aminouridine moiety plays a crucial role in the pharmacophore of sansanmycin. For expanding the structural diversity of the 5'-aminouridine moiety of sansanmycin through biosynthetic methods, we firstly demonstrated that SsaM and SsaK are responsible for the biosynthesis of the 5'-aminouridine moiety of sansanmycin in vivo. Using the ssaK deletion mutant (SS/KKO), we efficiently obtained a series of new analogues with modified 5'-aminouridine moieties through mutational biosynthesis. Based on molecular networking analysis of MS/MS, twenty-two new analogues (SS-KK-1 to -13 and SS-KK-A to -I) were identified. Among them, four new analogues (SS-KK-1 to -3 and SS-KK-C) were purified and bioassayed. SS-KK-2 showed better antibacterial activity against E. coli ΔtolC than the parent compound sansanmycin A. SS-KK-3 showed the same anti-TB activity as sansanmycin A against M. tuberculosis H37Rv as well as clinically isolated, drug-sensitive and multidrug-resistant M. tuberculosis strains. Furthermore, SS-KK-3 exhibited significantly improved structural stability compared to sansanmycin A. The results suggested that mutasynthesis is an effective and practical strategy for expanding the structural diversity of 5'-aminouridine moiety in sansanmycin.
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Negative public sentiment built up around bisphenol A (BPA) follows growing awareness of the frequency of this chemical compound in the environment. The increase in air, water, and soil contamination by BPA has also generated the need to replace it with less toxic analogs, such as Bisphenol F (BPF) and Bisphenol S (BPS). However, due to the structural similarity of BPF and BPS to BPA, questions arise about the safety of their usage. The toxicity of BPA, BPF, and BPS towards humans and animals has been fairly well understood. The biodegradability potential of microorganisms towards each of these bisphenols is also widely recognized. However, the scale of their inhibitory pressure on soil microbiomes and soil enzyme activity has not been estimated. These parameters are extremely important in determining soil health, which in turn also influences plant growth and development. Therefore, in this manuscript, knowledge has been expanded and systematized regarding the differences in toxicity between BPA and its two analogs. In the context of the synthetic characterization of the effects of bisphenol permeation into the environment, the toxic impact of BPA, BPF, and BPS on the microbiological and biochemical parameters of soils was traced. The response of cultivated plants to their influence was also analyzed.
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The isolation and identification of an increasing number of secondary metabolites featuring unique skeletons and possessing diverse bioactivities sourced from marine microorganisms have garnered the interest of numerous natural product chemists. There has been a growing emphasis on how to cultivate microorganisms to enhance the chemical diversity of metabolites and avoid the rediscovery of known ones. Given the significance of secondary metabolites as a means of communication among microorganisms, microbial co-culture has been introduced. By mimicking the growth patterns of microbial communities in their natural habitats, the co-culture strategy is anticipated to stimulate biosynthetic gene clusters that remain dormant under traditional laboratory culture conditions, thereby inducing the production of novel secondary metabolites. Different from previous reviews mainly focusing on fermentation conditions or metabolite diversities from marine-derived co-paired strains, this review covers the marine-derived co-culture microorganisms from 2012 to 2022, and turns to a particular discussion highlighting the selection of co-paired strains for marine-derived microorganisms, especially the fermentation methods for their co-cultural apparatus, and the screening approaches for the convenient and rapid detection of novel metabolites, as these are important in the co-culture. Finally, the structural and bioactivity diversities of molecules are also discussed. The challenges and prospects of co-culture are discussed on behave of the views of the authors.
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Produtos Biológicos , Microbiota , Técnicas de Cocultura , Aquicultura , FermentaçãoRESUMO
MAIN CONCLUSION: Biphenyl and dibenzofuran phytoalexins are differentially distributed among species of the rosaceous subtribe Malinae, which includes apple and pear, and exhibit varying inhibitory activity against phytopathogenic microorganisms. Biphenyls and dibenzofurans are specialized metabolites, which are formed in species of the rosaceous subtribe Malinae upon elicitation by biotic and abiotic inducers. The subtribe Malinae (previously Pyrinae) comprises approximately 1000 species, which include economically important fruit trees such as apple and pear. The present review summarizes the current status of knowledge of biphenyls and dibenzofurans in the Malinae, mainly focusing on their role as phytoalexins. To date, 46 biphenyls and 41 dibenzofurans have been detected in 44 Malinae species. Structurally, 54 simple molecules, 23 glycosidic compounds and 10 miscellaneous structures were identified. Functionally, 21 biphenyls and 21 dibenzofurans were demonstrated to be phytoalexins. Furthermore, their distribution in species of the Malinae, inhibitory activities against phytopathogens, and structure-activity relationships were studied. The most widely distributed phytoalexins of the Malinae are the three biphenyls aucuparin (3), 2'-methoxyaucuparin (7), and 4'-methoxyaucuparin (9) and the three dibenzofurans α-cotonefuran (47), γ-cotonefuran (49), and eriobofuran (53). The formation of biphenyl and dibenzofuran phytoalexins appears to be an essential defense weapon of the Malinae against various stresses. Manipulating phytoalexin formation may enhance the disease resistance in economically important fruit trees. However, this approach requires an extensive understanding of how the compounds are formed. Although the biosynthesis of biphenyls was partially elucidated, formation of dibenzofurans remains largely unclear. Thus, further efforts have to be made to gain deeper insight into the distribution, function, and metabolism of biphenyls and dibenzofurans in the Malinae.