Two structurally different oomycete lipophilic microbe-associated molecular patterns induce distinctive plant immune responses.

Plants recognize a variety of external signals and induce appropriate mechanisms to increase their tolerance to biotic and abiotic stresses. Precise recognition of attacking pathogens and induction of effective resistance mechanisms are critical functions for plant survival. Some molecular patterns unique to a certain group of microbes, microbe-associated molecular patterns (MAMPs), are sensed by plant cells as nonself molecules via pattern recognition receptors.

Botrytis cinerea detoxifies the sesquiterpenoid phytoalexin rishitin through multiple metabolizing pathways.

Botrytis cinerea is a necrotrophic pathogen that infects across a broad range of plant hosts, including high-impact crop species. Its generalist necrotrophic behavior stems from its ability to detoxify structurally diverse phytoalexins. The current study aims to provide evidence of the ability of B.

Molecular basis of N-glycan recognition by pradimicin a and its potential as a SARS-CoV-2 entry inhibitor.

Virus entry inhibitors are emerging as an attractive class of therapeutics for the suppression of viral transmission. Naturally occurring pradimicin A (PRM-A) has received particular attention as the first-in-class entry inhibitor that targets N-glycans present on viral surface. Despite the uniqueness of its glycan-targeted antiviral activity, there is still limited knowledge regarding how PRM-A binds to viral N-glycans.

tolerates phytoalexins produced by Solanaceae and Fabaceae plants through an efflux transporter BcatrB and metabolizing enzymes.

, a plant pathogenic fungus with a wide host range, has reduced sensitivity to fungicides as well as phytoalexins, threatening cultivation of economically important fruits and vegetable crops worldwide. tolerates a wide array of phytoalexins, through efflux and/or enzymatic detoxification. Previously, we provided evidence that a distinctive set of genes were induced in when treated with different phytoalexins such as rishitin (produced by tomato and potato), capsidiol (tobacco and bell pepper) and resveratrol (grape and blueberry).

Heterologous Biosynthesis of Myxobacterial Antibiotic Miuraenamide A.

The hard-to-culture slightly halophilic myxobacterium "" SMH-27-4 produces antifungal cyclodepsipeptide miuraenamide A (). Herein, the region (85.9 kbp) containing the biosynthetic gene cluster (BGC) coding the assembly of was identified and heterologously expressed in A biosynthetic pathway proposed using in silico analysis was verified through the gene disruption of the heterologous transformant.

Genomic Analysis of the Rare Slightly Halophilic Myxobacterium "" SMH-27-4, the Producer of the Antibiotic Miuraenamide A.

Halophilic/halotolerant myxobacteria are extremely rare bacteria but an important source of novel bioactive secondary metabolites as drug leads. A slightly halophilic myxobacterium, "" SMH-27-4, the producer of the antifungal antibiotic miuraenamide A, was considered to represent a novel genus. This study aimed to use the whole-genome sequence of this difficult-to-culture bacterium to provide genomic evidence supporting its taxonomy and to explore its potential as a novel secondary metabolite producer and its predicted gene functions.

identifies host plants via the recognition of antifungal capsidiol to induce expression of a specific detoxification gene.

The gray mold pathogen has a broad host range, causing disease in >400 plant species, but it is not known how this pathogen evolved this polyxenous nature. can metabolize a wide range of phytoalexins, including the stilbenoid resveratrol in grape, and the sesquiterpenoids capsidiol in tobacco and rishitin in potato and tomato. In this study, we analyzed the metabolism of sesquiterpenoid phytoalexins by .

Neuritogenic steroid glycosides from crown-of-thorns starfish: Possible involvement of p38 mitogen-activated protein kinase and attenuation of cognitive impairment in senescence-accelerated mice (SAMP8) by peripheral administration.

Novel steroid glycosides, acanthasterosides A1, B1, and B3, have been isolated from the crown-of-thorns starfish Acanthaster planci. Acanthasterosides B1 and B3 having two separated xyloses induced neurite outgrowth as like as nerve growth factor (NGF) in the rat pheochromocytoma cell line PC12, whereas acanthasteroside A1, having one xylose, did not induce neurite outgrowth. The acanthasteroside B3 induced neuritogenesis via the significant activation of p38 mitogen-activated protein kinase after the activation of the small G-protein Cdc42 rather than via Ras-MEK-ERK pathway that is predominantly activated by NGF.

Synthesis of aglycones, structure-activity relationships, and mode of action of lycosides as inhibitors of the asexual reproduction of Phytophthora.

Phytophthora are plant pathogens that damage agricultural products. Lycosides (1a-d), found in vegetable juice, have the potential to curb the rapid outbreak and crop damage caused by the asexual reproduction of Phytophthora. Here, aglycones 2a, b with slightly higher activity than lycosides were synthesized as a diastereomeric mixture (mix-2) possessing activity (IC50 = 4.

Inhibitors of Asexual Reproduction of the Plant Pathogen from Tomato Juice: Structure-Activity Relationships and Transcriptome Analysis.

is a genus of fungus-like microorganisms that damages important crops, such as potatoes and tomatoes. Its asexual reproduction, which results in the production of numerous motile zoospores, is the cause of quick and severe outbreaks and crop damage. The search for substances that selectively inhibit the asexual reproduction of led to the isolation of the known natural products naringenin and flazin from tomato juice.

Recognition of pathogen-derived sphingolipids in .

In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide -ceramide D (Pi-Cer D) from the plant pathogenic oomycete triggers defense responses in . Pi-Cer D is cleaved by an apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl-branched sphingoid base is recognized by a plasma membrane lectin receptor-like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2).

AP2/ERF Transcription Factor NbERF-IX-33 Is Involved in the Regulation of Phytoalexin Production for the Resistance of to .

Plants recognize molecular patterns unique to a certain group of microbes to induce effective resistance mechanisms. Elicitins are secretory proteins produced by plant pathogenic oomycete genera including and Treatment of INF1 (an elicitin produced by ) induces a series of defense responses in species, including reactive oxygen species (ROS) production, transient induction of ethylene production, hypersensitive cell death and accumulation of the sesquiterpenoid phytoalexin capsidiol. In this study, we analyzed the expression profiles of genes after INF1 treatment by RNAseq analysis.

d-Mannose binding, aggregation property, and antifungal activity of amide derivatives of pradimicin A.

Pradimicin A (PRM-A) and its derivatives comprise a unique family of antibiotics that show antifungal, antiviral, and antiparasitic activities through binding to d-mannose (Man)-containing glycans of pathogenic species. Despite their great potential as drug leads with an exceptional antipathogenic action, therapeutic application of PRMs has been severely limited by their tendency to form water-insoluble aggregates. Recently, we found that attachment of 2-aminoethanol to the carboxy group of PRM-A via amide linkage significantly suppressed the aggregation.

Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity.

Neurogenerative diseases, such as Parkinson's disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit toxic effects on neuronal cells. Both catecholic and aldehyde groups seem to be associated with the neurotoxicity of DOPAL.

A Pradimicin-Based Staining Dye for Glycoprotein Detection.

Pradimicin A (PRM-A) and related compounds constitute an exceptional family of natural pigments that show Ca-dependent recognition of d-mannose (Man). Although these compounds hold great promise as research tools in glycobiology, their practical application has been severely limited by their inherent tendency to form water-insoluble aggregates. Here, we demonstrate that the 2-hydroxyethylamide derivative (PRM-EA) of PRM-A shows little aggregation in neutral aqueous media and retains binding specificity for Man.

The Oxidation of Equol by Tyrosinase Produces a Unique Di--Quinone: Possible Implications for Melanocyte Toxicity.

Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman, EQ), one of the major intestinally derived metabolites of daidzein, the principal isoflavane found in soybeans and most soy foods, has recently attracted increased interest as a health-beneficial compound for estrogen-dependent diseases. However, based on its structure with two -substituted phenols, this study aimed to examine whether EQ is a substrate for tyrosinase and whether it produces -quinone metabolites that are highly cytotoxic to melanocyte. First, the tyrosinase-catalyzed oxidation of EQ was performed, which yielded three EQ-quinones.

Identification of biosynthetic intermediates for the mating hormone α2 of the plant pathogen Phytophthora.

The heterothallic group of the plant pathogen Phytophthora can sexually reproduce between the cross-compatible mating types A1 and A2. The mating hormone α2, produced by A2 mating type and utilized to promote the sexual reproduction of the partner A1 type, is known to be biosynthesized from phytol. In this study, we identified 2 biosynthetic intermediates, 11- and 16-hydroxyphytols (1 and 2), for α2 by administering the synthetic intermediates to an A2-type strain to produce α2 and by administering phytol to A2 strains to detect the intermediates in the mycelia.

Identification of ε-Poly-L-lysine as an Antimicrobial Product from an Endophyte and Isolation of Fungal ε-PL Synthetase Gene.

The endophytic fungus is known to produce bioactive metabolites, which consequently protect the host plants from biotic and abiotic stresses. We previously found that the overexpression of (a gene for transcription factor) in strain E437 resulted in the secretion of an unknown fungicide. In the present study, the active substance was purified and chemically identified as ε-poly-L-lysine (ε-PL), which consisted of 28-34 lysine units.

Relationship among structure, cytotoxicity, and Michael acceptor reactivity of quinocidin.

Quinocidin (QCD) is a cytotoxic antibiotic with an unusual 3,4-dihydroquinolizinium skeleton. We previously found that QCD captures thiols in neutral aqueous media via a Michael addition-type reaction. However, it remains unclear whether the Michael acceptor reactivity of QCD is responsible for its cytotoxicity.

Detoxification of the solanaceous phytoalexins rishitin, lubimin, oxylubimin and solavetivone via a cytochrome P450 oxygenase.

Solanaceous plants produce sesquiterpenoid phytoalexins to defend themselves against a variety of pathogens. These toxic compounds are not only harmful to the pathogen but also to the plant, and thus need to be detoxified by the plant after the threat has been eliminated. We report that the detoxification of rishitin, the major phytoalexin in potato tubers and tomato fruits, is mediated by a cytochrome P450 CYP76 family enzyme via the hydroxylation of the isopropenyl group resulting in the formation of 13-hydroxyrishitin, also known as rishitin-M1.

Tyrosinase-catalyzed oxidation of resveratrol produces a highly reactive ortho-quinone: Implications for melanocyte toxicity.

trans-Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RES), a naturally occurring polyphenol, has recently attracted increased interest as a health-beneficial agent. However, based on its p-substituted phenol structure, RES is expected to be a substrate for tyrosinase and to produce a toxic o-quinone metabolite. The results of this study demonstrate that the oxidation of RES by tyrosinase produces 4-(3',5'-dihydroxy-trans-styrenyl)-1,2-benzoquinone (RES-quinone), which decays rapidly to an oligomeric product (RES-oligomer).

Clavariopsins C-I, Antifungal Cyclic Depsipeptides from the Aquatic Hyphomycete .

Seven new cyclic depsipeptides, clavariopsins C-I (-), together with two known congeners, clavariopsins A and B ( and ), were isolated from the aquatic hyphomycete . Their planar structures, which consist of nine amino acids and one α-hydroxy acid, were elucidated by NMR spectroscopy and HRESIMS. The absolute configurations were established by the advanced Marfey's method and chiral-phase HPLC analysis.

The Oxidative Pathway to Dopamine-Protein Conjugates and Their Pro-Oxidant Activities: Implications for the Neurodegeneration of Parkinson's Disease.

Neuromelanin (NM) is a dark brown pigment found in dopaminergic neurons of the substantia nigra (SN) and in norepinephrinergic neurons of the locus coeruleus (LC). Although NM is thought to be involved in the etiology of Parkinson's disease (PD) because its content decreases in neurodegenerative diseases such as PD, details are still unknown. In this study, we characterized the biosynthetic pathway of the oxidation of dopamine (DA) by tyrosinase in the presence of thiol peptides and proteins using spectroscopic and high-performance liquid chromatography (HPLC) methods and we assessed the binding of DA via cysteine residues in proteins by oxidation catalyzed by redox-active metal ions.

Molecular Basis of Mannose Recognition by Pradimicins and their Application to Microbial Cell Surface Imaging.

Naturally occurring pradimicins (PRMs) show specific recognition of d-mannose (d-Man) in aqueous media, which has never been achieved by artificial small molecules. Although the Ca-mediated dimerization of PRMs is essential for their d-Man binding, the dimeric structure has yet to be elucidated, leaving the question open as to how PRMs recognize d-Man. Thus, we herein report the structural elucidation of the dimer by a combination of X-ray crystallography and solid-state NMR spectroscopy.

RanBP1-1 Is Involved in the Induction of Disease Resistance via Regulation of Nuclear-Cytoplasmic Transport of Small GTPase Ran.

Plant cells enhance the tolerances to abiotic and biotic stresses via recognition of the stress, activation and nuclear import of signaling factors, up-regulation of defense genes, nuclear export of mRNA and translation of defense proteins. Nuclear pore-mediated transports should play critical roles in these processes, however, the regulatory mechanisms of nuclear-cytoplasmic transport during stress responses are largely unknown. In this study, a regulator of nuclear export of RNA and proteins, NbRanBP1-1 (Ran-binding protein1-1), was identified as an essential gene for the resistance of to potato blight pathogen .