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Antimicrobial Agents and Chemotherapy May 1979Fourteen polyene antibiotics and six of their semisynthetic derivatives were compared for their effects on potassium (K(+)) leakage and lethality or hemolysis of either...
Fourteen polyene antibiotics and six of their semisynthetic derivatives were compared for their effects on potassium (K(+)) leakage and lethality or hemolysis of either Saccharomyces cerevisiae or mouse erythrocytes. These polyene antibiotics fell into two groups. Group I antibiotics caused K(+) leakage and cell death or hemolysis at the same concentrations of added polyene. In this group fungistatic and fungicidal levels were indistinguishable. Group I drugs included one triene (trienin); tetraenes (pimaricin and etruscomycin); pentaenes (filipin and chainin); one hexaene (dermostatin); and one polyene antibiotic with unknown chemical structure (lymphosarcin). Group II antibiotics caused considerable K(+) leakage at low concentrations and cell death or hemolysis at high concentrations. The fungistatic levels were clearly separable from fungicidal. This group included the heptaenes (amphotericin B, candicidin, aureofungin A and B, hamycin A and B), and five of their semisynthetic derivatives (amphotericin B methyl ester, N-acetyl-amphotericin B, hamycin A and B methyl esters, and N-acetyl-candicidin). Nystatin, classified as a tetraene, and its derivative, N-acetyl nystatin, also were in this group.
Topics: Animals; Antifungal Agents; Chemical Phenomena; Chemistry; Erythrocytes; In Vitro Techniques; Mice; Polyenes; Potassium; Saccharomyces cerevisiae; Structure-Activity Relationship
PubMed: 393163
DOI: 10.1128/AAC.15.5.716 -
Journal of the American Chemical Society Dec 20171,3-Dienes are ubiquitous and easily synthesized starting materials for organic synthesis, and alkyl acrylates are among the most abundant and cheapest feedstock carbon...
1,3-Dienes are ubiquitous and easily synthesized starting materials for organic synthesis, and alkyl acrylates are among the most abundant and cheapest feedstock carbon sources. A practical, highly enantioselective union of these two readily available precursors giving valuable, enantio-pure skipped 1,4-diene esters (with two configurationally defined double bonds) is reported. The process uses commercially available cobalt salts and chiral ligands. As illustrated by the use of 20 different substrates, including 17 prochiral 1,3-dienes and 3 acrylates, this hetero-dimerization reaction is tolerant of a number of common organic functional groups (e.g., aromatic substituents, halides, isolated mono- and di-substituted double bonds, esters, silyl ethers, and silyl enol ethers). The novel results including ligand, counterion, and solvent effects uncovered during the course of these investigations show a unique role of a possible cationic Co(I) intermediate in these reactions. The rational evolution of a mechanism-based strategy that led to the eventual successful outcome and the attendant support studies may have further implications for the expanding use of low-valent group 9 metal complexes in organic synthesis.
Topics: Acrylates; Catalysis; Cobalt; Dimerization; Esters; Ethers; Ligands; Polyenes
PubMed: 29120629
DOI: 10.1021/jacs.7b10055 -
Journal of Oleo Science Dec 2018The surface and interfacial properties of casein-hydrolyzed peptides were evaluated using measurement of surface and interfacial tensions, surface viscosity, dynamic...
The surface and interfacial properties of casein-hydrolyzed peptides were evaluated using measurement of surface and interfacial tensions, surface viscosity, dynamic light scattering (DLS), and freeze-fracture transmission electron microscopy (FF-TEM). In this study, high internal oil phase emulsion (HIPE) gels were successfully prepared, using the surface and interfacial properties of casein peptides. The casein peptides exhibited surface and interfacial activities. The estimated critical micelle concentration (CMC) and γ values were 3.0 mg/mL and 47.8 mN/m, and the average size of casein peptide micelles was 13.2 ± 1.7 nm. The surface shear viscosity of an aqueous casein peptide solution at 10 mg/mL was 1603 µPa ms, which is fifteen times larger than that of sodium dodecyl sulfate (SDS, 106 µPa ms). The larger surface viscosity of casein peptide adsorbed layer could stabilize emulsions and prevent flocculation and coalescence. High internal oil phase gel emulsions were then prepared by slowly adding oil and polyisobutene into an aqueous casein peptide solution/glycerol mixture with different compositions. Based on the pseudo ternary 15 wt% aqueous casein peptide solution/polyisobutene/glycerol phase diagram, the HIPE containing the maximum 88.1 wt% (91.5 vol%) of oil is obtained by the addition of 0.36 wt% of casein peptides. The use of only a small amount of protein-hydrolyzed peptides instead of the commonly used synthetic surfactants for HIPE preparation has great advantages for the widespread application of HIPE technology.
Topics: Caseins; Emulsions; Gels; Micelles; Oils; Particle Size; Peptide Fragments; Polyenes; Polymers; Surface Tension; Viscosity
PubMed: 30429446
DOI: 10.5650/jos.ess18140 -
Scientific Reports Apr 2021Some Gram-negative bacteria harbor lipids with aryl polyene (APE) moieties. Biosynthesis gene clusters (BGCs) for APE biosynthesis exhibit striking similarities with... (Comparative Study)
Comparative Study
Some Gram-negative bacteria harbor lipids with aryl polyene (APE) moieties. Biosynthesis gene clusters (BGCs) for APE biosynthesis exhibit striking similarities with fatty acid synthase (FAS) genes. Despite their broad distribution among pathogenic and symbiotic bacteria, the detailed roles of the metabolic products of APE gene clusters are unclear. Here, we determined the crystal structures of the β-ketoacyl-acyl carrier protein (ACP) reductase ApeQ produced by an APE gene cluster from clinically isolated virulent Acinetobacter baumannii in two states (bound and unbound to NADPH). An in vitro visible absorption spectrum assay of the APE polyene moiety revealed that the β-ketoacyl-ACP reductase FabG from the A. baumannii FAS gene cluster cannot be substituted for ApeQ in APE biosynthesis. Comparison with the FabG structure exhibited distinct surface electrostatic potential profiles for ApeQ, suggesting a positively charged arginine patch as the cognate ACP-binding site. Binding modeling for the aryl group predicted that Leu185 (Phe183 in FabG) in ApeQ is responsible for 4-benzoyl moiety recognition. Isothermal titration and arginine patch mutagenesis experiments corroborated these results. These structure-function insights of a unique reductase in the APE BGC in comparison with FAS provide new directions for elucidating host-pathogen interaction mechanisms and novel antibiotics discovery.
Topics: 3-Oxoacyl-(Acyl-Carrier-Protein) Reductase; Acinetobacter baumannii; Amino Acid Sequence; Arginine; Biosynthetic Pathways; Crystallography, X-Ray; Fatty Acids; Leucine; Models, Molecular; NADP; Polyenes; Protein Conformation; Static Electricity; Structural Homology, Protein; Substrate Specificity
PubMed: 33846444
DOI: 10.1038/s41598-021-86997-3 -
Molecules (Basel, Switzerland) Sep 2021Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of...
Being a methyl ester of partricin, the mepartricin complex is the active substance of a drug called Ipertrofan (Tricandil), which was proven to be useful in treatment of benign prostatic hyperplasia and chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Nevertheless, no direct structural evidence on the stereochemistry of its components has been presented to date. In this contribution, we have conducted detailed, NMR-driven stereochemical studies on mepartricins A and B, aided by molecular dynamics simulations. The absolute configuration of all the stereogenic centers of mepartricin A and B was defined as 3, 7, 9, 11, 13, 15, 17, 18, 19, 21, 36, 37, and 38, and proposed as 41. The geometry of the heptaenic chromophore of both compounds has been established as 22, 24, 26, 28, 30, 32, and 34. Our studies on mepartricin ultimately proved that partricins A and B are structurally identical to the previously described main components of the aureofacin complex: gedamycin and vacidin, respectively. The knowledge of the stereochemistry of this drug is a fundamental matter not only in terms of studies on its molecular mode of action, but also for potential derivatization, aiming at improvement of its pharmacological properties.
Topics: Magnetic Resonance Spectroscopy; Mepartricin; Molecular Dynamics Simulation; Polyenes; Stereoisomerism; Terminology as Topic; Urological Agents
PubMed: 34577003
DOI: 10.3390/molecules26185533 -
Molecules (Basel, Switzerland) May 2017Based on the total π-electron energies s of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C₂H₂) up to = 7,...
Based on the total π-electron energies s of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C₂H₂) up to = 7, the structure-stability relation of the possible isomers was analyzed. It was shown that the mean length of conjugation can roughly predict the ordering of stability among isomers, while the -index, or Hosoya-index, can almost perfectly reproduce their stability. Further, the genealogy of the conjugated acyclic polyene family was obtained by drawing systematic diagrams connecting these isomers of different , and governed by several simple rules. Namely, the stability change of a given isomer in the genealogy connecting and + 1 polyenes can be classified into three different modes of vinyl addition (elongation, inner and outer branching) and horn growing, i.e., substitution of -HC=CH- moiety with -HC(=CH₂)-C(=CH₂)H-. By using the -index, we can extend this type of discussion to polyene radicals and even to "cross-conjugated" cyclic polyenes containing only one odd-membered cycle, such as radialene and fulvene.
Topics: Models, Molecular; Molecular Structure; Polyenes
PubMed: 28555053
DOI: 10.3390/molecules22060896 -
Journal of Natural Products May 2017Marine algae from the genus Karlodinium are known to be involved in fish-killing events worldwide. Here we report for the first time the chemistry and bioactivity of a...
Marine algae from the genus Karlodinium are known to be involved in fish-killing events worldwide. Here we report for the first time the chemistry and bioactivity of a natural product from the newly described mixotrophic dinoflagellate Karlodinium armiger. Our work describes the isolation and structural characterization of a new polyhydroxy-polyene named karmitoxin. The structure elucidation work was facilitated by use of C enrichment and high-field 2D NMR spectroscopy, where H-C long-range correlations turned out to be very informative. Karmitoxin is structurally related to amphidinols and karlotoxins; however it differs by containing the longest carbon-carbon backbone discovered for this class of compounds, as well as a primary amino group. Karmitoxin showed potent nanomolar cytotoxic activity in an RTgill-W1 cell assay as well as rapid immobilization and eventual mortality of the copepod Acartia tonsa, a natural grazer of K. armiger.
Topics: Amines; Animals; Dinoflagellida; Magnetic Resonance Spectroscopy; Marine Toxins; Molecular Structure; Polyenes
PubMed: 28379705
DOI: 10.1021/acs.jnatprod.6b00860 -
Brazilian Journal of Microbiology :... 2016Candida albicans is the primary causative agent of oral candidosis, and one of its key virulent attributes is considered to be its ability to produce extracellular...
Extracellular phospholipase production of oral Candida albicans isolates from smokers, diabetics, asthmatics, denture wearers and healthy individuals following brief exposure to polyene, echinocandin and azole antimycotics.
OBJECTIVE
Candida albicans is the primary causative agent of oral candidosis, and one of its key virulent attributes is considered to be its ability to produce extracellular phospholipases that facilitate cellular invasion. Oral candidosis can be treated with polyenes, and azoles, and the more recently introduced echinocandins. However, once administered, the intraoral concentration of these drugs tend to be sub-therapeutic and rather transient due to factors such as the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, the pathogenic yeasts may undergo a brief exposure to antifungal drugs. We, therefore, evaluated the phospholipase production of oral C. albicans isolates following brief exposure to sub-therapeutic concentrations of the foregoing antifungals.
MATERIALS AND METHODS
Fifty C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sub-therapeutic concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for one hour. Thereafter the drugs were removed and the phospholipase production was determined by a plate assay using an egg yolk-agar medium.
RESULTS
The phospholipase production of these isolates was significantly suppressed with a percentage reduction of 10.65, 12.14, 11.45 and 6.40% following exposure to nystatin, amphotericin B, caspofungin and ketoconazole, respectively. This suppression was not significant following exposure to fluconazole.
CONCLUSIONS
Despite the sub-therapeutic, intra oral, bioavailability of polyenes, echinocandins and ketoconazole, they are likely to produce a persistent antifungal effect by suppressing phospholipase production, which is a key virulent attribute of this common pathogenic yeast.
Topics: Antifungal Agents; Azoles; Candida albicans; Candidiasis, Oral; Dentures; Diabetes Mellitus; Echinocandins; Enzyme Activation; Extracellular Space; Humans; Microbial Sensitivity Tests; Phospholipases; Polyenes; Smoking; Virulence Factors
PubMed: 27522928
DOI: 10.1016/j.bjm.2016.06.009 -
Cell Oct 2017Parrot feathers contain red, orange, and yellow polyene pigments called psittacofulvins. Budgerigars are parrots that have been extensively bred for plumage traits...
Parrot feathers contain red, orange, and yellow polyene pigments called psittacofulvins. Budgerigars are parrots that have been extensively bred for plumage traits during the last century, but the underlying genes are unknown. Here we use genome-wide association mapping and gene-expression analysis to map the Mendelian blue locus, which abolishes yellow pigmentation in the budgerigar. We find that the blue trait maps to a single amino acid substitution (R644W) in an uncharacterized polyketide synthase (MuPKS). When we expressed MuPKS heterologously in yeast, yellow pigments accumulated. Mass spectrometry confirmed that these yellow pigments match those found in feathers. The R644W substitution abolished MuPKS activity. Furthermore, gene-expression data from feathers of different bird species suggest that parrots acquired their colors through regulatory changes that drive high expression of MuPKS in feather epithelia. Our data also help formulate biochemical models that may explain natural color variation in parrots. VIDEO ABSTRACT.
Topics: Amino Acid Sequence; Animals; Avian Proteins; Feathers; Gene Expression; Genome; Genome-Wide Association Study; Melopsittacus; Pigmentation; Pigments, Biological; Polyenes; Polyketide Synthases; Polymorphism, Single Nucleotide; Regeneration; Sequence Alignment
PubMed: 28985565
DOI: 10.1016/j.cell.2017.08.016 -
Microbial Cell Factories Feb 2023Streoptomyces rimosus M527 is a producer of the polyene macrolide rimocidin which shows activity against various plant pathogenic fungi. Notably, the regulatory...
BACKGROUND
Streoptomyces rimosus M527 is a producer of the polyene macrolide rimocidin which shows activity against various plant pathogenic fungi. Notably, the regulatory mechanisms underlying rimocidin biosynthesis are yet to be elucidated.
RESULTS
In this study, using domain structure and amino acid alignment and phylogenetic tree construction, rimR2, which located in the rimocidin biosynthetic gene cluster, was first found and identified as a larger ATP-binding regulators of the LuxR family (LAL) subfamily regulator. The rimR2 deletion and complementation assays were conducted to explore its role. Mutant M527-ΔrimR2 lost its ability to produce rimocidin. Complementation of M527-ΔrimR2 restored rimocidin production. The five recombinant strains, M527-ER, M527-KR, M527-21R, M527-57R, and M527-NR, were constructed by overexpressing rimR2 gene using the promoters permE, kasOp, SPL21, SPL57, and its native promoter, respectively, to improve rimocidin production. M527-KR, M527-NR, and M527-ER exhibited 81.8%, 68.1%, and 54.5% more rimocidin production, respectively, than the wild-type (WT) strain, while recombinant strains M527-21R and M527-57R exhibited no obvious differences in rimocidin production compared with the WT strain. RT-PCR assays revealed that the transcriptional levels of the rim genes were consistent with the changes in rimocidin production in the recombinant strains. Using electrophoretic mobility shift assays, we confirmed that RimR2 can bind to the promoter regions of rimA and rimC.
CONCLUSION
A LAL regulator RimR2 was identified as a positive specific-pathway regulator of rimocidin biosynthesis in M527. RimR2 regulates the rimocidin biosynthesis by influencing the transcriptional levels of rim genes and binding to the promoter regions of rimA and rimC.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Phylogeny; Polyenes; Streptomyces rimosus
PubMed: 36810073
DOI: 10.1186/s12934-023-02039-9