Variety Of Secondary Metabolites Research Articles

A comparative phytochemical study of nine Lauraceae species by using chemometric data analysis.

The diversity of secondary metabolites of individual plants results from multiple enzymatic processes in planta and various environmental factors, such as temperature, moisture, and soil conditions. Chemical composition analysis of plants can lead to a new method to understand relationship among comparable plants along with biological classification such as genetic and anatomical method. In this study, the chemical diversity of nine different Lauraceae species was investigated, and the plant samples were chemically analyzed and classified. Multivariate analysis methods, such as PLS-DA, were used to select important metabolites distinguishing the nine Lauraceae species. The selected metabolites were identified through preparative LC-MS or MS/MS fragment pattern analysis. In addition, the chemical dendrogram for the nine Lauraceae species was interpreted through molecular network analysis and compared with the genetic dendrogram. This approach enabled us to compare the complete chemical compositions of multiple plant samples to identify relationships among plants.

Secondary metabolites from the mangrove soil derived fungus Xylariaceae sp. SCSIO41212

ObjectiveTo obtain structurally novel and bioactive secondary metabolites from the marine fungus Xylariaceae sp. SCSIO41212. MethodsCompounds were purified by comprehensive chromatography methods of silica gel column, Sephadex LH-20, Ostade-cylsilane (ODS) and semi-preparative HPLC, and their structures were elucidated by means of physical and chemical properties, magnefic resonance imaging, spectroscopic analysis, and comparison with the reported literatures. ResultsChemical investigation of the fungus Xylariaceae sp. SCSIO41212 has led to the isolation of two new compounds, xylaolide B (1) and xylaolide C (2), together with nine known compounds (3–11). Their structures were determined on the basis of detailed analysis of the 1D and 2D NMR as well as MS data. Compounds 1–6 were evaluated for their antiviral, and cytotoxic activities, respectively. Compound 1 showed weak cytotoxicities against K562, MCF-7 and SGC7901 respectively. ConclusionThis study enriches the diversity of secondary metabolites of marine-derived fungi and provides an important reference for novel promising drug leads research.

Unraveling usnic acid: a comparison of biosynthetic gene clusters between two reindeer lichen (Cladonia rangiferina and C. uncialis)

Lichenized fungi are known for their production of a diversity of secondary metabolites, many of which have broad biological and pharmacological applications. By far the most well-studied of these metabolites is usnic acid. While this metabolite has been well-known and researched for decades, the gene cluster responsible for its production was only recently identified from the species Cladonia uncialis. Usnic acid production varies considerably in the genus Cladonia, even among closely related taxa, and many species, such as C. rangiferina, have been inferred to be incapable of producing the metabolite based on analysis by thin-layer chromatography (TLC). We sequenced and examined the usnic acid biosynthetic gene clusters, or lack thereof, from four closely related Cladonia species (C. oricola, C. rangiferina, C. stygia, and C. subtenuis), and compare them against those of C. uncialis. We complement this comparison with tiered chemical profile analyses to confirm the presence or absence of usnic acid in select samples, using both HPLC and LC-MS. Despite long-standing reporting that C. rangiferina lacks the ability to produce usnic acid, we observed functional gene clusters from the species and detected usnic acid when extracts were examined by LC-MS. By contrast, C. stygia and C. oricola, have been previously described as lacking the ability to produce usnic acid, lacked the gene cluster entirely, and no usnic acid could be detected in C. oricola extracts via HPLC or LC-MS. This work suggests that chemical profiles attained through inexpensive and low-sensitivity methods like TLC may fail to detect low abundance metabolites that can be taxonomically informative. This study also bolsters understanding of the usnic acid gene cluster in lichens, revealing differences among domains of the polyketide synthase which may explain observed differences in expression. These results reinforce the need for comprehensive characterization of lichen secondary metabolite profiles with sensitive LC-MS methods.

Glycoside-specific metabolomics combined with precursor isotopic labeling for characterizing plant glycosyltransferases

Glycosylation by uridine diphosphate-dependent glycosyltransferases (UGTs) in plants contributes to the complexity and diversity of secondary metabolites. UGTs are generally promiscuous in their use of acceptors, making it challenging to reveal the function of UGTs in vivo. Here, we described an approach that combined glycoside-specific metabolomics and precursor isotopic labeling analysis to characterize UGTs in Arabidopsis. We revisited the UGT72E cluster, which has been reported to catalyze the glycosylation of monolignols. Glycoside-specific metabolomics analysis reduced the number of differentially accumulated metabolites in the ugt72e1e2e3 mutant by at least 90% compared with that from traditional untargeted metabolomics analysis. In addition to the two previously reported monolignol glycosides, a total of 62 glycosides showed reduced accumulation in the ugt72e1e2e3 mutant, 22 of which were phenylalanine-derived glycosides, including 5-OH coniferyl alcohol-derived and lignan-derived glycosides, as confirmed by isotopic tracing of [13C6]-phenylalanine precursor. Our method revealed that UGT72Es could use coumarins as substrates, and genetic evidence showed that UGT72Es endowed plants with enhanced tolerance to low iron availability under alkaline conditions. Using the newly developed method, the function of UGT78D2 was also evaluated. These case studies suggest that this method can substantially contribute to the characterization of UGTs and efficiently investigate glycosylation processes, the complexity of which have been highly underestimated.

Unusual Secondary Metabolites from the Mangrove Ecosystems: Structures, Bioactivities, Chemical, and Bio-Syntheses

Mangrove ecosystems are widely distributed in the intertidal zone of tropical and subtropical estuaries or coasts, containing abundant biological communities, for example, mangrove plants and diverse groups of microorganisms, featuring various bioactive secondary metabolites. We surveyed the literature from 2010 to 2022, resulting in a collection of 134 secondary metabolites, and classified them into two major families in terms of the biological sources and 15 subfamilies according to the chemical structures. To highlight the structural diversity and bioactivities of the mangrove ecosystem-associated secondary metabolites, we presented the chemical structures, bioactivities, biosynthesis, and chemical syntheses.

Volatile-Mediated Induced and Passively Acquired Resistance in Sagebrush (Artemisia tridentata)

Plants produce a diversity of secondary metabolites including volatile organic compounds. Some species show discrete variation in these volatile compounds such that individuals within a population can be grouped into distinct chemotypes. A few studies reported that volatile-mediated induced resistance is more effective between plants belonging to the same chemotype and that chemotypes are heritable. The authors concluded that the ability of plants to differentially respond to cues from related individuals that share the same chemotype is a form of kin recognition. These studies assumed plants were actively responding but did not test the mechanism of resistance. A similar result was possible through the passive adsorption and reemission of repellent or toxic VOCs by plants exposed to damage-induced plant volatiles (DIPVs). Here we conducted exposure experiments with five chemotypes of sagebrush in growth chambers; undamaged receiver plants were exposed to either filtered air or DIPVs from mechanically wounded branches. Receiver plants exposed to DIPVs experienced less herbivore damage, which was correlated with increased expression of genes involved in plant defense as well as increased emission of repellent VOCs. Plants belonging to two of the five chemotypes exhibited stronger resistance when exposed to DIPVs from plants of the same chemotypes compared to when DIPVs were from plants of a different chemotype. Moreover, some plants passively absorbed DIPVs and reemitted them, potentially conferring associational resistance. These findings support previous work demonstrating that sagebrush plants actively responded to alarm cues and that the strength of their response was dependent on the chemotypes of the plants involved. This study provides further support for kin recognition in plants but also identified volatile-mediated associational resistance as a passively acquired additional defense mechanism in sagebrush.

6,7-dimethoxydihydrocoumarin Compound from Ethyl Acetate Extracts from Steambarks Dysoxylum Alliaceum and Cytotoxic Activity Against P-388

Dysoxylum is a genus that has a variety of secondary metabolites. Research on various species of this genus is always growing and producing compounds that have interesting structures and activities, until now many compounds of the terpenoid group, chroman alkaloids, limonoids, sesquiterpenes, flavonoids, steroids, protolimonoids and sulfur have been reported. which is very interesting. One of the Dysoxylum species that has a variety of secondary metabolites is D. alliaceum. The purpose of this study was to obtain secondary metabolites of D. alliaceum bark. The bark of D. alliaceum was macerated successively with n-hexane, ethyl acetate and methanol. The ethyl acetate extract was separated and purified by various chromatographic techniques and was characterized using spectroscopic methods including, ultraviolet, infrared, NMR and mass spectroscopy and guided by thin layer chromatographic analysis to obtain the compound 6,7-dimethoxydyhidrocoumarin and the proposed biogenesis. The chemical structure of these compounds has been determined based on the interpretation of spectroscopic data and compared with spectral data from previous studies. Cytotoxic activity test against P-388 MTT leukemia cells obtained an IC50 of 39.210 g/mL and was declared inactive.

HISTOCHEMICAL ANALYSIS OF THE LEAVES OF FOUR ERICALES MEDICINAL PLANTS

Active chemical compounds from medicinal plants are mostly secondary metabolites that can be histochemically tested. It enables the identification and localization of diverse secondary metabolites within the tissue, which is not possible with screening phytochemicals. In this study, the histochemistry of the leaf blades of Ericales plants i.e., cantigi (Vaccinium varingiaefolium (Blume) Miq.), persimmon (Diospyros kaki Thunb.), sapodilla (Manilkara zapota (L.) van Royen), and star apple (Chrysophyllum cainito L.) were evaluated. These species have been reported as folk medicines that have secondary metabolites. Each leaf tissue was observed under a microscope, and phytochemical compounds presence and location were detected by using specific reagents. The results showed that those four leaves contained phenols, flavonoids, and terpenes, while quinones were only found in cantigi leaves. The secondary metabolites were present in the idioblast of parenchymal and epidermal tissues. The persimmon and star apple leaves had secretory cavities in trichomes with terpenes and phenolic compounds.

Metabolomics of Non-Saccharomyces Yeasts in Fermented Beverages

Fermented beverages have been consumed for millennia and today support a global industry producing diverse products. Saccharomyces yeasts currently dominate the fermented beverage industry, but consumer demands for alternative products with a variety of sensory profiles and actual or perceived health benefits are driving the diversification and use of non-Saccharomyces yeasts. The diversity of flavours, aromas, and other sensory characteristics that can be obtained by using non-Saccharomyces yeasts in fermentation is, in large part, due to the diverse secondary metabolites they produce compared to conventional Saccharomyces yeast. Here, we review the use of metabolomic analyses of non-Saccharomyces yeasts to explore their impact on the sensory characteristics of fermented beverages. We highlight several key species currently used in the industry, including Brettanomyces, Torulaspora, Lachancea, and Saccharomycodes, and emphasize the future potential for the use of non-Saccharomyces yeasts in the production of diverse fermented beverages.

Light Spectrum Effects on the Ions, and Primary and Secondary Metabolites of Red Beets (Beta vulgaris L.)

Red beet (Beta vulgaris L.) is a root vegetable consumed and cultivated all around the world. It contains plenty of sugars, inorganic ions and a variety of secondary metabolites known to improve human health. The aim of this work was to investigate the effect of light spectra on red beets and their components in a vertical farm (VF) compared to open field (OF). RED (red:blue-white = 4:1)-treated shoots elevated total phenolic contents (TPC) among lights. Sugar content in VF red beets was 4.2 times higher than beets from OF. Betalains in VF red beets were 2.4–2.8 times higher than OF ones, and RED-treated roots had significantly higher betalain levels compared to CON (red:blue-white = 2:1)-treated ones. VF red beets contained a higher level of inorganic nitrates and lower chloride compared to OF beets. In conclusion, the light spectrum alters the concentration of beet components to be higher than that of OF red beets, and RED light elevated TPC, sugars and betalains.

Morphology and phytochemical diversity among some species in the Cyperaceae family

Classification of members of Cyperaceae is complicated basically due to the size and complexity of their inflorescences. This study employed morphological attributes to delimit some species belonging to the Cyperus, Pycreus, Mariscus, Kyllinga, Fimbristylis, and Rhynchospora; and further explored and analyzed the secondary metabolites from these species if they could be helpful in their characterization. Eighteen morphological characters were considered and analyzed through cluster analysis. Additionally, thin layer chromatography (TLC) was employed to screen phytochemicals such as flavonoid, steroid, tannin, saponin, triterpene, alkaloid, and cardiac glycosides in some of the sedges. The morphological study showed that the cluster analysis grouped all the species studied into two main clusters. The first main cluster contained all the Cyperus species studied except C. nipponus and C. rotundus. However, a few members of other genera studied were embedded within the Cyperus cluster. On the other hand, the second main cluster was further divided into two sub-clusters; the first sub-cluster had only Fimbristylis species while the second sub-cluster comprised Kyllinga, Pycreus, Mariscus species and two Cyperus species. In this present study, the inflorescence type and achene morphology played a significant role in delimiting the accessions studied. The TLC profiling of the species of Cyperaceae studied revealed their phytochemical diversity which can be harnessed in pharmaceutical industries. Moreover, the phytochemicals detected (flavonoid, steroid, tannin, saponin, triterpene, alkaloid, and cardiac glycosides) have been demonstrated to be useful in the delimitation of the species within each genus studied and elucidated the relationship that exists among them. However, they have little or no taxonomic value in delimiting the genera studied within the family Cyperaceae. Further research is required with respect to the characterization of the diverse secondary metabolites detected in some members of Cyperaceae studied

Phytochemical Screening and In Vitro Antifungal Activity of Selected Medicinal Plants against Candida albicans and Aspergillus niger in West Shewa Zone, Ethiopia.

Antimicrobial resistance to commercially available medications has become a global issue, yet there is still the possibility of developing new drugs from medicinal plants. As a result, the aims of the present study were to screen secondary metabolites and to evaluate in vitro antifungal activities of Brucea antidysenterica, Aloe vera, and Justicia schimperiana. After the plants were identified, their leaves were collected, washed, dried under the shade, pulverized, and extracted with methanol (99.8%) using the maceration technique. The presence of secondary metabolites in plant extracts was screened using various laboratory protocols. The antifungal activities of the plant extract against reference fungal strains of Candida albicans and Aspergillus niger at concentrations of 200, 100, and 50 mg/mL were assessed using the agar-well diffusion method. Ketoconazole (15 μg) was used as a positive control, while 5% dimethyl sulfoxide and/or 5% Tween 80 were used as negative controls. All tests were conducted in triplicate. Alkaloids, flavonoids, and phenols were secondary metabolites found in all plant extracts. The extract of leaves of B. antidysenterica and J. schimperiana formed a mean zone of inhibition of 15.5 ± 0.5 mm and 15.3 ± 0.58 mm, respectively, against Candida albicans at a concentration of 200 mg/mL, whereas extracts of A. vera leaves formed a 12.3 ± 0.58 mm inhibition zone only against Aspergillus niger at 200 mg/mL. In conclusion, the current study found that B. antidysenterica, A. vera, and J. schimperiana had antifungal activity. In addition, all these plants had a variety of secondary metabolites that possibly have antifungal activities. Studies on in vivo investigations and isolation of specific antifungal compounds from these medicinal plants are suggested.

Cultivar-specific miRNA-mediated RNA silencing in grapes.

In-depth comparative degradome analysis of two domesticated grape cultivars with diverse secondary metabolite accumulation reveals differential miRNA-mediated targeting. Small (s)RNAs such as micro(mi)RNAs and secondary small interfering (si) often work as negative switches of gene expression. In plants, it is well known that miRNAs target and cleave mRNAs that have high sequence complementarity. However, it is not known if there are variations in miRNA-mediated targeting between subspecies and cultivars that have been subjected to vast genetic modifications through breeding and other selections. Here, we have used PAREsnip2 tool for analysis of degradome datasets derived from two contrasting domesticated grape cultivars having varied fruit color, habit and leaf shape. We identified several interesting variations in sRNA targeting using degradome and 5'RACE analysis between two contrasting grape cultivars that was further correlated using RNA-seq analysis. Several of the differences we identified are associated with secondary metabolic pathways. We propose possible means by which sRNAs might contribute to diversity in secondary metabolites and other development pathways between two domesticated cultivars of grapes.

Plant Host Traits Mediated by Foliar Fungal Symbionts and Secondary Metabolites.

Fungal symbionts living inside plant leaves ("endophytes") can vary from beneficial to parasitic, but the mechanisms by which the fungi affect the plant host phenotype remain poorly understood. Chemical interactions are likely the proximal mechanism of interaction between foliar endophytes and the plant, as individual fungal strains are often exploited for their diverse secondary metabolite production. Here, we go beyond single strains to examine commonalities in how 16 fungal endophytes shift plant phenotypic traits such as growth and physiology, and how those relate to plant metabolomics profiles. We inoculated individual fungi on switchgrass, Panicum virgatum L. This created a limited range of plant growth and physiology (2-370% of fungus-free controls on average), but effects of most fungi overlapped, indicating functional similarities in unstressed conditions. Overall plant metabolomics profiles included almost 2000 metabolites, which were broadly correlated with plant traits across all the fungal treatments. Terpenoid-rich samples were associated with larger, more physiologically active plants and phenolic-rich samples were associated with smaller, less active plants. Only 47 metabolites were enriched in plants inoculated with fungi relative to fungus-free controls, and of these, Lasso regression identified 12 metabolites that explained from 14 to 43% of plant trait variation. Fungal long-chain fatty acids and sterol precursors were positively associated with plant photosynthesis, conductance, and shoot biomass, but negatively associated with survival. The phytohormone gibberellin, in contrast, was negatively associated with plant physiology and biomass. These results can inform ongoing efforts to develop metabolites as crop management tools, either by direct application or via breeding, by identifying how associations with more beneficial components of the microbiome may be affected.

Sulfur-Containing Compounds from Endophytic Fungi: Sources, Structures and Bioactivities.

Endophytic fungi have attracted increasing attention as an under-explored source for the discovery and development of structurally and functionally diverse secondary metabolites. These microorganisms colonize their hosts, primarily plants, and demonstrate diverse ecological distribution. Among endophytic fungal natural products, sulfur-containing compounds feature one or more sulfur atoms and possess a range of bioactivities, e.g., cytotoxicity and antimicrobial activities. These natural products mainly belong to the classes of polyketides, nonribosomal peptides, terpenoids, and hybrids. Here, we reviewed the fungal producers, plant sources, chemical structures, and bioactivities of 143 new sulfur-containing compounds that were reported from 1985 to March 2022.

Intradiol ring cleavage dioxygenases from herbivorous spider mites as a new detoxification enzyme family in animals

BackgroundGeneralist herbivores such as the two-spotted spider mite Tetranychus urticae thrive on a wide variety of plants and can rapidly adapt to novel hosts. What traits enable polyphagous herbivores to cope with the diversity of secondary metabolites in their variable plant diet is unclear. Genome sequencing of T. urticae revealed the presence of 17 genes that code for secreted proteins with strong homology to “intradiol ring cleavage dioxygenases (DOGs)” from bacteria and fungi, and phylogenetic analyses show that they have been acquired by horizontal gene transfer from fungi. In bacteria and fungi, DOGs have been well characterized and cleave aromatic rings in catecholic compounds between adjacent hydroxyl groups. Such compounds are found in high amounts in solanaceous plants like tomato, where they protect against herbivory. To better understand the role of this gene family in spider mites, we used a multi-disciplinary approach to functionally characterize the various T. urticae DOG genes.ResultsWe confirmed that DOG genes were present in the T. urticae genome and performed a phylogenetic reconstruction using transcriptomic and genomic data to advance our understanding of the evolutionary history of spider mite DOG genes. We found that DOG expression differed between mites from different plant hosts and was induced in response to jasmonic acid defense signaling. In consonance with a presumed role in detoxification, expression was localized in the mite’s gut region. Silencing selected DOGs expression by dsRNA injection reduced the mites’ survival rate on tomato, further supporting a role in mitigating the plant defense response. Recombinant purified DOGs displayed a broad substrate promiscuity, cleaving a surprisingly wide array of aromatic plant metabolites, greatly exceeding the metabolic capacity of previously characterized microbial DOGs.ConclusionOur findings suggest that the laterally acquired spider mite DOGs function as detoxification enzymes in the gut, disarming plant metabolites before they reach toxic levels. We provide experimental evidence to support the hypothesis that this proliferated gene family in T. urticae is causally linked to its ability to feed on an extremely wide range of host plants.

Natural products from Photorhabdus and Xenorhabdus: mechanisms and impacts.

Insects and fungal pathogens pose constant problems to public health and agriculture, especially in resource-limited parts of the world; and the use of chemical pesticides continues to be the main methods for the control of these organisms. Photorhabdus spp. and Xenorhabdus spp., (Fam; Morganellaceae), enteric symbionts of Steinernema, and Heterorhabditis nematodes are naturally found in soil on all continents, except Antarctic, and on many islands throughout the world. These bacteria produce diverse secondary metabolites that have important biological and ecological functions. Secondary metabolites include non-ribosomal peptides, polyketides, and/or hybrid natural products that are synthesized using polyketide synthetase (PRS), non-ribosomal peptide synthetase (NRPS), or similar enzymes and are sources of new pesticide/drug compounds and/or can serve as lead molecules for the design and synthesize of new alternatives that could replace current ones. This review addresses the effects of these bacterial symbionts on insect pests, fungal phytopathogens, and animal pathogens and discusses the substances, mechanisms, and impacts on agriculture and public health. KEY POINTS: • Insects and fungi are a constant menace to agricultural and public health. • Chemical-based control results in resistance development. • Photorhabdus and Xenorhabdus are compelling sources of biopesticides.

Desulfoluna spp. form a cosmopolitan group of anaerobic dehalogenating bacteria widely distributed in marine sponges.

Host-specific microbial communities thrive within sponge tissues and this association between sponge and associated microbiota may be driven by the organohalogen chemistry of the sponge animal. Several sponge species produce diverse organobromine secondary metabolites (e.g. brominated phenolics, indoles, and pyrroles) that may function as a chemical defense against microbial fouling, infection or predation. In this study, anaerobic cultures prepared from marine sponges were amended with 2,6-dibromophenol as the electron acceptor and short chain organic acids as electron donors. We observed reductive dehalogenation from diverse sponge species collected at disparate temperate and tropical waters suggesting that biogenic organohalides appear to enrich for populations of dehalogenating microorganisms in the sponge animal. Further enrichment by successive transfers with 2,6-dibromophenol as the sole electron acceptor demonstrated the presence of dehalogenating bacteria in over 20 sponge species collected from temperate and tropical ecoregions in the Atlantic and Pacific Oceans and the Mediterranean Sea. The enriched dehalogenating strains were closely related to Desulfoluna spongiiphila and Desulfoluna butyratoxydans, suggesting a cosmopolitan association between Desulfoluna spp. and various marine sponges. In vivo reductive dehalogenation in intact sponges was also demonstrated. Organobromide-rich sponges may thus provide a specialized habitat for organohalide-respiring microbes and D. spongiiphila and/or its close relatives are responsible for reductive dehalogenation in geographically widely distributed sponge species.

Exploring the Relationship between Trichome and Terpene Chemistry in Chrysanthemum.

Chrysanthemum is a popular ornamental plant with a long history of cultivation. Both the leaf and flowerhead of Chrysanthemum are known to produce diverse secondary metabolites, particularly terpenoids. Here we aimed to determine the relationship between terpene chemistry and the trichome traits in Chrysanthemum. In our examination of three cultivars of C. morifilium and three accessions of C. indicum, all plants contained T-shaped trichomes and biseriate peltate glandular trichomes. The biseriate peltate glandular trichome contained two basal cells, two stalk cells, six secondary cells and a subcuticular space, while the non-glandular T-shaped trichome was only composed of stalk cells and elongated cells. Histochemical staining analysis indicated that the biseriate peltate glandular trichome contained terpenoids and lipid oil droplets but not the T-shaped trichome. Next, experiments were performed to determine the relationship between the accumulation and emission of the volatile terpenoids and the density of trichomes on the leaves and flowerheads in all six Chrysanthemum cultivars\\accessions. A significant correlation was identified between the monoterpenoid and sesquiterpenoid content and the density of glandular trichomes on the leaves, with the correlation coefficients being 0.88, 0.86 and 0.90, respectively. In contrast, there was no significant correlation between the volatile terpenoid content and the density of T-shaped trichomes on the leaves. In flowerheads, a significant correlation was identified between the emission rate of terpenoids and the number of glandular trichomes on the disc florets, with a correlation coefficient of 0.95. Interestingly, the correlation between the density of glandular trichomes and concentrations of terpenoids was insignificant. In summary, the relationship between trichomes and terpenoid chemistry in Chrysanthemum is clearly established. Such knowledge may be helpful for breeding aromatic Chrysanthemum cultivars by modulating the trichome trait.

Phenazines and toxoflavin act as interspecies modulators of resilience to diverse antibiotics.

Bacterial opportunistic pathogens make diverse secondary metabolites both in the natural environment and when causing infections, yet how these molecules mediate microbial interactions and their consequences for antibiotic treatment are still poorly understood. Here, we explore the role of three redox-active secondary metabolites, pyocyanin, phenazine-1-carboxylic acid, and toxoflavin, as interspecies modulators of antibiotic resilience. We find that these molecules dramatically change susceptibility levels of diverse bacteria to clinical antibiotics. Pyocyanin and phenazine-1-carboxylic acid are made by Pseudomonas aeruginosa, while toxoflavin is made by Burkholderia gladioli, organisms that infect cystic fibrosis and other immunocompromised patients. All molecules alter the susceptibility profile of pathogenic species within the "Burkholderia cepacia complex" to different antibiotics, either antagonizing or potentiating their effects, depending on the drug's class. Defense responses regulated by the redox-sensitive transcription factor SoxR potentiate the antagonistic effects these metabolites have against fluoroquinolones, and the presence of genes encoding SoxR and the efflux systems it regulates can be used to predict how these metabolites will affect antibiotic susceptibility of different bacteria. Finally, we demonstrate that inclusion of secondary metabolites in standard protocols used to assess antibiotic resistance can dramatically alter the results, motivating the development of new tests for more accurate clinical assessment.