-
Journal of Industrial Microbiology &... Jun 2013Polyene macrolides are a large family of natural products typically produced by soil actinomycetes. Polyene macrolides are usually biosynthesized by modular and large... (Review)
Review
Polyene macrolides are a large family of natural products typically produced by soil actinomycetes. Polyene macrolides are usually biosynthesized by modular and large type I polyketide synthases (PKSs), followed by several steps of sequential post-PKS modifications such as region-specific oxidations and glycosylations. Although known as powerful antibiotics containing potent antifungal activities (along with additional activities against parasites, enveloped viruses and prion diseases), their high toxicity toward mammalian cells and poor distribution in tissues have led to the continuous identification and structural modification of polyene macrolides to expand their general uses. Advances in in-depth investigations of the biosynthetic mechanism of polyene macrolides and the genetic manipulations of the polyene biosynthetic pathways provide great opportunities to generate new analogues. Recently, a novel class of polyene antibiotics was discovered (a disaccharide-containing NPP) that displays better pharmacological properties such as improved water-solubility and reduced hemolysis. In this review, we summarize the recent advances in the biosynthesis, pathway engineering, and regulation of polyene antibiotics in actinomycetes.
Topics: Actinobacteria; Animals; Anti-Bacterial Agents; Antifungal Agents; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Genetic Engineering; Glycosylation; Hemolysis; Macrolides; Polyenes; Polyketide Synthases
PubMed: 23515854
DOI: 10.1007/s10295-013-1258-6 -
Chemistry (Weinheim An Der Bergstrasse,... Aug 2021Polyene cyclizations generate molecular complexity from a linear polyene in a single step. While methods to initiate these cyclizations have been continuously expanded...
Polyene cyclizations generate molecular complexity from a linear polyene in a single step. While methods to initiate these cyclizations have been continuously expanded and improved over the years, the majority of polyene substrates are still limited to simple alkyl-substituted alkenes. In this study, we took advantage of the unique reactivity of higher-functionalized bifunctional alkenes. The realization of a polyene tetracyclization of a dual nucleophilic aryl enol ether involving a transannular endo-termination step enabled the total synthesis of the tricyclic diterpenoid pimara-15-en-3α-8α-diol. The highly flexible and modular route allowed for the preparation of a diverse library of cyclization precursors specifically designed for the total synthesis of the tetracyclic nor-diterpenoid norflickinflimiod C. The tetracyclization of three diversely substituted allenes enabled access to complex pentacyclic products and provided a detailed insight into the underlying reaction pathways.
Topics: Abietanes; Biological Products; Cyclization; Polyenes; Stereoisomerism
PubMed: 34213030
DOI: 10.1002/chem.202101926 -
Progress in Medicinal Chemistry 1977
Review
Topics: Animals; Anti-Bacterial Agents; Chemical Phenomena; Chemistry; Drug Interactions; Drug Resistance, Microbial; Eukaryotic Cells; Fungi; Humans; In Vitro Techniques; Membranes; Polyenes; Sterols
PubMed: 345355
DOI: 10.1016/s0079-6468(08)70148-6 -
Molecules (Basel, Switzerland) Mar 2023Six new polyene carboxylic acids named serpentemycins E-J (-), together with three known analogs (-), were isolated from the fermentation medium of sp. TB060207, which...
Six new polyene carboxylic acids named serpentemycins E-J (-), together with three known analogs (-), were isolated from the fermentation medium of sp. TB060207, which was isolated from arid soil collected from Tibet, China. The structures of the new compounds were elucidated mainly on the basis of HR-ESI-MS and NMR spectroscopic analyses. The inhibitory activities of compounds - against NO production in LPS-activated RAW264.7 cells were evaluated. Compound has an inhibition rate of 87.09% to 60.53% at concentrations ranging from 5.0 to 40.0 µM.
Topics: Carboxylic Acids; Tibet; Streptomyces; Magnetic Resonance Spectroscopy; Polyenes
PubMed: 36985551
DOI: 10.3390/molecules28062579 -
Fortschritte Der Chemie Organischer... 1963
Review
Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antifungal Agents; Chemistry, Pharmaceutical; Dermatologic Agents; Polyenes
PubMed: 14287136
DOI: 10.1007/978-3-7091-7149-3_2 -
Science (New York, N.Y.) Feb 1955
Topics: Anti-Bacterial Agents; Polyenes; Spectrum Analysis
PubMed: 13225759
DOI: 10.1126/science.121.3136.147 -
Biochimica Et Biophysica Acta Dec 1986In the 1970's great strides were made in understanding the mechanism of action of amphotericin B and nystatin: the formation of transmembrane pores was clearly... (Review)
Review
In the 1970's great strides were made in understanding the mechanism of action of amphotericin B and nystatin: the formation of transmembrane pores was clearly demonstrated in planar lipid monolayers, in multilamellar phospholipid vesicles and in Acholeplasma laidlawii cells and the importance of the presence and of the nature of the membrane sterol was analyzed. For polyene antibiotics with shorter chains, a mechanism of membrane disruption was proposed. However, recently obtained data on unilamellar vesicles have complicated the situation. It has been shown that: membranes in the gel state (which is not common in cells), even if they do not contain sterols may be made permeable by polyene antibiotics, several mechanisms may operate, simultaneously or sequentially, depending on the antibiotic/lipid ratio, the time elapsed after mixing and the mode of addition of the antibiotic, there is a rapid exchange of the antibiotic molecules between the vesicles. Although pore formation is apparently involved in the toxicity of amphotericin B and nystatin, it is not the sole factor which contributes to cell death, since K+ leakage induced by these antibiotics is separate from their lethal action. The peroxidation of membrane lipids, which has been demonstrated for erythrocytes and Candida albicans cells in the presence of amphotericin B, may play a determining role in toxicity concurrently with colloid osmotic effect. On the other hand, it has been shown that the action of polyene antibiotics on cells is not always detrimental: at sub-lethal concentrations these drugs stimulate either the activity of some membrane enzymes or cellular metabolism. In particular, some cells of the immune system are stimulated. Furthermore, polyene antibiotics may act synergistically with other drugs, such as antitumor or antifungal compounds. This may occur either by an increased incorporation of the drug, under the influence of a polyene antibiotic-induced change of membrane potential, for example, or by a direct interaction of both drugs. That fungal membranes contain ergosterol while mammalian cell membranes contain cholesterol, has generally been considered the basis for the selective toxicity of amphotericin B and nystatin for fungi. Actually, in vitro studies have not always borne out this assumption, thereby casting doubt on the use of polyene antibiotics as antifungal agents in mammalian cell culture media.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Cell Line; Cell Membrane; Cell Membrane Permeability; Filipin; Humans; Lucensomycin; Nystatin; Polyenes
PubMed: 3539192
DOI: 10.1016/0304-4157(86)90002-x -
Organic & Biomolecular Chemistry Oct 2014This review provides insight into the variety of structures and biological activities found in the non-isoprenoid family of polyene natural products and examines the... (Review)
Review
This review provides insight into the variety of structures and biological activities found in the non-isoprenoid family of polyene natural products and examines the strategies and synthetic methods applied for the polyenic components in particular by way of examples.
Topics: Biological Products; Molecular Structure; Polyenes
PubMed: 25188767
DOI: 10.1039/c4ob01337a -
Journal of Global Antimicrobial... Jun 2018Environmental fungicides are used in agriculture to reduce fungal spoilage of crops to a minimum, and the polyene macrolide natamycin is used as a food preservative. The... (Review)
Review
Environmental fungicides are used in agriculture to reduce fungal spoilage of crops to a minimum, and the polyene macrolide natamycin is used as a food preservative. The use of natamycin in yoghurt has recently been authorised in the USA and some other countries. However, resistance development is a serious risk associated with the use of antimicrobials as food additives and environmental fungicides. Cross-resistance between agricultural and medical azoles and between azoles and amphotericin B (AMB) not being used in agriculture has been demonstrated in clinical and environmental isolates. Polyene resistance can be elicited in vitro by the use of subinhibitory polyene concentrations and a large number of transfers. This condition may mirror the exposure of faecal Candida spp. to natamycin following consumption of natamycin-containing food. A large number of environmental and clinical isolates are resistant to AMB, and strong evidence linking farm antibiotic use and multidrug resistance, including AMB resistance, in human infections has been provided. In contrast to the acquisition of resistant environmental strains, consumption of natamycin-containing food may expose the gastrointestinal fungal flora directly to resistance selective pressure. So far, whether natamycin itself may cause the emergence of polyene resistance in gastrointestinal fungal flora and/or may act as an AMB resistance selector is probable but speculative. Use of any anti-infective agent as a food preservative should be limited to an absolute minimum as the clinical efficacy of anti-infectives used to treat serious life-threatening infections has to be preserved.
Topics: Agriculture; Antifungal Agents; Drug Resistance, Fungal; Drug Utilization; Food Industry; Fungi; Humans; Polyenes; Selection, Genetic
PubMed: 29127020
DOI: 10.1016/j.jgar.2017.10.024 -
Organic Letters Mar 2022A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a...
A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a ruthenium-catalyzed step-economic and environmentally benign strategy for the highly stereo- and chemoselective construction of valuable polyene motifs of FR252921 and vitamin A highlights the syntheses. The key features for the synthesis FR252921 include preparation of the triene moiety followed by two consecutive peptide couplings of the three fragments.
Topics: Biological Products; Lactams; Lactones; Polyenes; Vitamin A
PubMed: 35274951
DOI: 10.1021/acs.orglett.2c00546