The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Rapamycin is also a macrolide and was originally developed as an antifungal, but is now used as an immunosuppressant drug and is being investigated as a potential longevity therapeutic.
ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). ATP synthase is a molecular machine. The overall reaction catalyzed by ATP synthase is:
The myxobacteria are a group of bacteria that predominantly live in the soil and feed on insoluble organic substances. The myxobacteria have very large genomes relative to other bacteria, e.g. 9–10 million nucleotides except for Anaeromyxobacter and Vulgatibacter. One species of myxobacteria, Minicystis rosea, has the largest known bacterial genome with over 16 million nucleotides. The second largest is another myxobacteria Sorangium cellulosum.
The bafilomycins are a family of macrolide antibiotics produced from a variety of Streptomycetes. Their chemical structure is defined by a 16-membered lactone ring scaffold. Bafilomycins exhibit a wide range of biological activity, including anti-tumor, anti-parasitic, immunosuppressant and anti-fungal activity. The most used bafilomycin is bafilomycin A1, a potent inhibitor of cellular autophagy. Bafilomycins have also been found to act as ionophores, transporting potassium K+ across biological membranes and leading to mitochondrial damage and cell death.
Vacuolar-type ATPase (V-ATPase) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pumps protons across the plasma membranes of numerous cell types. V-ATPases couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. It is generally seen as the polar opposite of ATP synthase because ATP synthase is a proton channel that uses the energy from a proton gradient to produce ATP. V-ATPase however, is a proton pump that uses the energy from ATP hydrolysis to produce a proton gradient.
Tolypocladium inflatum is an ascomycete fungus originally isolated from a Norwegian soil sample that, under certain conditions, produces the immunosuppressant drug ciclosporin. In its sexual stage (teleomorph) it is a parasite on scarab beetles. It forms a small, compound ascocarp that arises from the cadaver of its host beetle. In its asexual stage (anamorph) it is a white mold that grows on soil. It is much more commonly found in its asexual stage and this is the stage that was originally given the name Tolypocladium inflatum.
The inorganic dye ammoniated ruthenium oxychloride, also known as ruthenium red, is used in histology to stain aldehyde fixed mucopolysaccharides.
Sorangium cellulosum is a soil-dwelling Gram-negative bacterium of the group myxobacteria. It is motile and shows gliding motility. Under stressful conditions this motility, as in other myxobacteria, the cells congregate to form fruiting bodies and differentiate into myxospores. These congregating cells make isolation of pure culture and colony counts on agar medium difficult as the bacterium spread and colonies merge. It has an unusually-large genome of 13,033,779 base pairs, making it the largest bacterial genome sequenced to date by roughly 4 Mb.
Peroxiredoxin-5 (PRDX5), mitochondrial is a protein that in humans is encoded by the PRDX5 gene, located on chromosome 11.
ATP synthase subunit e, mitochondrial is an enzyme that in humans is encoded by the ATP5ME gene.
ATP synthase F1 subunit epsilon, mitochondrial is an enzyme that in humans is encoded by the ATP5F1E gene. The protein encoded by ATP5F1E is a subunit of ATP synthase, also known as Complex V. Variations of this gene have been associated with mitochondrial complex V deficiency, nuclear 3 (MC5DN3) and Papillary Thyroid Cancer.
A quinone methide is a type of conjugated organic compound that contain a cyclohexadiene with a carbonyl and an exocyclic methylidene or extended alkene unit. It is analogous to a quinone, but having one of the double bonded oxygens replaced with a carbon. The carbonyl and methylidene are usually oriented either ortho or para to each other. There are some examples of transient synthetic meta quinone methides.
Stigmatella aurantiaca is a member of myxobacteria, a group of gram-negative bacteria with a complex developmental life cycle.
Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol, which stabilizes microtubules, or Phalloidin, which stabilizes actin filaments. Others, such as Cytochalasin D, bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed microtubules. Some of these drugs have multiple effects on the cytoskeleton: for example, Latrunculin both prevents actin polymerization as well as enhancing its rate of depolymerization. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer. As a result of the lack of specificity for specific type of actin, the use of these drugs in animals results in unacceptable off-target effects. Despite this, the actin targeting compounds are still useful tools that can be used on a cellular level to help further our understanding of how this complex part of the cells' internal machinery operates. For example, Phalloidin that has been conjugated with a fluorescent probe can be used for visualizing the filamentous actin in fixed samples.
Gephyronic acid is a polyketide that exists as an equilibrating mixture of structural isomers. In nature, gephyronic acid is produced by slow growing myxobacterium: Archangium gephyra strain Ar3895 and Cystobacter violaceus strain Cb vi76. It is the first antibiotic in myxobacteria that was reported to specifically inhibit eukaryotic protein synthesis.
Ossamycin is a fermentation-derived natural product belonging to a family of 22- to 26-membered macrocyclic polyketides which is featured with a 6,6-spiroacetal (1,7-dioxaspiro[5,5]-undecanyl) moiety connected to one side of the macrocycle. Widely-studied 26-membered oligomycins/rutamycins, 24-membered dunaimycins, and 22-membered cytovaricin are also in this family.
Chlorotonil A is a polyketide natural product produced by the myxobacterium Sorangium cellulosum So ce1525. It displays antimalarial activity in an animal model, and has in vitro antibacterial and antifungal activity. The activity of chlorotonil A has been attributed to the gem-dichloro-1,3-dione moiety, which is a unique functionality in polyketides. In addition to its unique halogenation, the structure of chlorotonil A has also garnered interest due to its similarity to anthracimycin, a polyketide natural product with antibiotic activity against Gram-positive bacteria.
Aureothin is a natural product of a cytotoxic shikimate-polyketide antibiotic with the molecular formula C22H23NO6. Aureothin is produced by the bacterium Streptomyces thioluteus that illustrates antitumor, antifungal, and insecticidal activities and the new aureothin derivatives can be antifungal and antiproliferative. In addition, aureothin, a nitro compound from Streptomyces thioluteus, was indicated to have pesticidal activity against the bean weevil by interfering with mitochondrial respiratory complex II.
