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Organic & Biomolecular Chemistry Jun 2022Alternapyrone is a highly methylated polyene α-pyrone biosynthesised by a highly reducing polyketide synthase. Mutations of the catalytic dyad residues, H1578A/Q and...
Alternapyrone is a highly methylated polyene α-pyrone biosynthesised by a highly reducing polyketide synthase. Mutations of the catalytic dyad residues, H1578A/Q and E1604A, of the -methyltransferase domain resulted in either significantly reduced or no production of alternapyrone, indicating the importance of -methylation for alternapyrone biosynthesis.
Topics: Methylation; Polyenes; Polyketide Synthases; Triterpenes
PubMed: 35695066
DOI: 10.1039/d2ob00947a -
Chemistry & Biology May 2005In this issue of Chemistry & Biology, Francisco Malpartida and colleagues [1] report the formation of novel polyene amide derivatives upon transformation of the producer...
In this issue of Chemistry & Biology, Francisco Malpartida and colleagues [1] report the formation of novel polyene amide derivatives upon transformation of the producer strain with SCP2*-derived vectors carrying the erythromycin resistance gene ermE. This unexpected finding provides a new tool for generating antifungal drugs by biotransformation.
Topics: Antifungal Agents; Drug Design; Macrolides; Methyltransferases; Monosaccharides; Polyenes; Polyketide Synthases; Streptomyces
PubMed: 15911369
DOI: 10.1016/j.chembiol.2005.05.002 -
Organic Letters Apr 2009Polyene cyclization of the titled compounds under catalysis with AlCl(3)/SnCl(4) gave rise to the corresponding polycyclic products, many of which were structurally...
Polyene cyclization of the titled compounds under catalysis with AlCl(3)/SnCl(4) gave rise to the corresponding polycyclic products, many of which were structurally highly unexpected, and thus, individual X-ray analysis was required to finalize the structural identification. Mechanistically, an unusual 1,2-hydride shift is proposed to elucidate the product formation.
Topics: Aluminum Chloride; Aluminum Compounds; Catalysis; Chlorides; Crystallography, X-Ray; Cyclization; Cyclohexanones; Molecular Structure; Polycyclic Compounds; Polyenes; Stereoisomerism; Tin Compounds
PubMed: 19354316
DOI: 10.1021/ol802878t -
Marine Drugs Aug 2013Separacenes A-D (1-4), novel polyene polyols, were isolated from Streptomyces sp. collected from the southern area of Jeju Island, Korea. The chemical structures of 1-4... (Comparative Study)
Comparative Study
Separacenes A-D (1-4), novel polyene polyols, were isolated from Streptomyces sp. collected from the southern area of Jeju Island, Korea. The chemical structures of 1-4 were established by NMR, mass, UV, and IR spectroscopy as well as the modified Mosher's method. Separacenes A-B (1-2), which share an identical planar structure but possess different relative configurations, bear tetraene units flanked by two diol moieties, whereas the stereoisomeric separacenes C-D (3-4) possess a triene moiety between two diol substructures. Separacenes A-D each contain a terminal olefinic methylene. Separacene A displayed inhibitory activity against Candida albicans isocitrate lyase and weak cytotoxicity against both the colon carcinoma cell line HCT-116 and the lung cancer cell line A549.
Topics: Antifungal Agents; Antineoplastic Agents; Candida albicans; Cell Line, Tumor; Colonic Neoplasms; HCT116 Cells; Humans; Lung Neoplasms; Polyenes; Polymers; Republic of Korea; Spectrum Analysis; Streptomyces
PubMed: 23945600
DOI: 10.3390/md11082882 -
PloS One 2012Recently, we showed that the effect of dipole modifiers (flavonoids and styrylpyridinium dyes) on the conductance of single amphotericin B (AmB) channels in...
Recently, we showed that the effect of dipole modifiers (flavonoids and styrylpyridinium dyes) on the conductance of single amphotericin B (AmB) channels in sterol-containing lipid bilayers primarily resulted from changes in the membrane dipole potential. The present study examines the effect of dipole modifiers on the AmB multi-channel activity. The addition of phloretin to cholesterol-containing membranes leads to a significant increase in the steady-state AmB-induced transmembrane current. Quercetin significantly decreases and RH 421 increases the current through ergosterol-containing bilayers. Other tested flavonoids and styrylpyridinium dyes do not affect the channel-forming activity of AmB independently on the sterol composition of the bilayers. The effects obtained in these trials may instead be attributed to the direct interaction of dipole modifiers with AmB/sterol complexes and not to the effect of dipole potential changes. The presence of double bonds in the Δ7 and Δ22 positions of sterol molecules, the number of conjugated double bonds and amino sugar residues in polyene molecules, and the conformation and adsorption plane of dipole modifiers are important factors impacting this interaction.
Topics: Amphotericin B; Coloring Agents; Electricity; Flavonoids; Ion Channel Gating; Lipid Bilayers; Polyenes; Sterols
PubMed: 23028805
DOI: 10.1371/journal.pone.0045135 -
Lipids Oct 1978Polyene antibiotics are useful tools for studying the role of sterols in biological membranes. The interaction of polyene antibiotics with membrane-bound sterols in...
Polyene antibiotics are useful tools for studying the role of sterols in biological membranes. The interaction of polyene antibiotics with membrane-bound sterols in artificial membrane systems, prokaryotic and eukaryotic cells, and lipid-containing viruses is reviewed. The pentaene macrolide, filipin, is shown to serve as a probe of phosphatidylcholine-sterol interaction and of the localization of cholesterol in the membrane of mycoplasmas.
Topics: Amphotericin B; Cholesterol; Filipin; Kinetics; Membranes; Mycoplasma; Phosphatidylcholines; Polyenes
PubMed: 723481
DOI: 10.1007/BF02533746 -
Bioorganic & Medicinal Chemistry May 2002The synthesis of two tetraenes that differ in their methylation pattern from the natural substrate in lanosterol biosynthesis, 2,3-oxidosqualene, and their examination...
The synthesis of two tetraenes that differ in their methylation pattern from the natural substrate in lanosterol biosynthesis, 2,3-oxidosqualene, and their examination with three catalytic antibodies is described. The design of these novel, linear terpenoid structures was governed by initial results obtained from the characterization of the three catalytic antibodies. These were generated by immunization with a steroidal hapten that mimics multicyclization without the necessity for anti-Markovnikov additions or ring expansions. Such a reaction cascade would represent a more 'primitive' version compared to the oxidosqualene cyclization observed in lanosterol, cycloartenol and beta-amyrin biosynthesis and would not require a tail-to-tail connection of the third and fourth isoprene unit as seen in squalene. The first tetraene design (A) only contains trisubstituted double bonds and hence its synthesis starts from farnesol and tris-norgeraniol. The second tetraene design (B) is considered the more precise match to the inducing hapten that generated the antibody collections by exhibiting one disubstituted double bond and its synthesis utilizes a tris-norgeraniol derivative and a symmetrical bis-allylic alcohol as key building blocks. Chromatographic comparison studies lead to the conclusion that the currently studied antibodies also produce monocyclic products from the two substrates as has been formerly observed with a squalene-derived substrate. In contrast, 2,3-oxidosqualene is not accepted by these catalysts supporting the notion that the current substrates are fully bound by recognition of both terminal functional groups.
Topics: Antibodies, Catalytic; Catalytic Domain; Cyclization; Haptens; Methylation; Molecular Probes; Polyenes; Substrate Specificity
PubMed: 11886788
DOI: 10.1016/s0968-0896(01)00402-3 -
International Journal of Molecular... Nov 2022are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may... (Review)
Review
are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by is presented.
Topics: Humans; Streptomyces; Antifungal Agents; Anti-Bacterial Agents; Polyenes; Hemolysis; Virulence Factors
PubMed: 36499372
DOI: 10.3390/ijms232315045 -
Physical Chemistry Chemical Physics :... Jul 2015Ab initio multiconfigurational quantum chemical methodology combined with molecular mechanics (CASPT2//CASSCF/AMBER) was applied to probe impacts of retinal protonated...
Ab initio multiconfigurational quantum chemical methodology combined with molecular mechanics (CASPT2//CASSCF/AMBER) was applied to probe impacts of retinal protonated Schiff base (RPSB) polyene methylation and/or demethylation on the mechanism of photochemical isomerization in bovine rhodopsin. We have examined structural and spectroscopic properties of wild-type rhodopsin (with 11-cis-9,13-dimethyl-RPSB) and artificial rhodopsins, hosting four 11-cis-RPSB derivatives, 13-demethyl-, 9-demethyl-, 10-methyl-13-demethyl-, and 10-methyl-RPSB, evolving along the photoisomerization coordinate. It is found that the addition of 10-methyl or/and deletion of 9-/13-methyl groups do not appear to interfere structurally with the photoisomerization pathway in the S1 excited state. Remarkably, the two-mode space-saving mechanism initiated by bond order inversion and followed by asynchronous bicycle-pedal distortion in the RPSB backbone drives the photoreaction in all rhodopsin analogues studied here. However, methylation and/or demethylation is responsible for perturbation of excess energy deposited in the conical intersection structures. The analysis of photon energy stored by bathorhodopsin in synthetic pigments reveals that it is affected by steric crowding of methyl substituents in the RPSB backbone.
Topics: Animals; Cattle; Methylation; Molecular Structure; Photochemical Processes; Photons; Polyenes; Quantum Theory; Rhodopsin; Stereoisomerism
PubMed: 26074351
DOI: 10.1039/c5cp01939g -
Organic Letters Feb 2012Fucoxanthin exhibits high energy transfer efficiencies to Chlorophyll a (Chl a) in photosynthesis in the sea. In order to reveal how each characteristic functional...
Fucoxanthin exhibits high energy transfer efficiencies to Chlorophyll a (Chl a) in photosynthesis in the sea. In order to reveal how each characteristic functional group, such as the length of the polyene chain, allene, and conjugated carbonyl groups, of this marine natural product are responsible for its remarkably efficient ability, the total synthesis of fucoxanthin by controlling the stereochemistry was achieved. The method established for fucoxanthin synthesis was successfully applied to the synthesis of the C42 longer chain analogue.
Topics: Molecular Structure; Polyenes; Stereoisomerism; Sulfones; Xanthophylls
PubMed: 22256969
DOI: 10.1021/ol203344c