Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken by mouth or by injection into a vein for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca.
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by bacteria, fungi, or plants which are not directly involved in the normal growth, development, or reproduction of the organism. Instead, they generally mediate ecological interactions, which may produce a selective advantage for the organism by increasing its survivability or fecundity. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavourings, pigments, and recreational drugs.
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or better bioactivity.
A natural product is a chemical compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.
Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi, from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later.
Gingerol, properly as [6]-gingerol, is a phenol phytochemical compound found in fresh ginger that activates spice receptors on the tongue. Molecularly, gingerol is a relative of capsaicin and piperine, the compounds which are alkaloids, though the bioactive pathways are unconnected. It is normally found as a pungent yellow oil in the ginger rhizome, but can also form a low-melting crystalline solid. This chemical compound is found in all members of the Zingiberaceae family and is high in concentrations in the grains of paradise as well as an African Ginger species.
Cyanidin is a natural organic compound. It is a particular type of anthocyanidin. It is a pigment found in many red berries including grapes, bilberry, blackberry, blueberry, cherry, chokeberry, cranberry, elderberry, hawthorn, loganberry, açai berry and raspberry. It can also be found in other fruits such as apples and plums, and in red cabbage and red onion. It has a characteristic reddish-purple color, though this can change with pH; solutions of the compound are red at pH < 3, violet at pH 7-8, and blue at pH > 11. In certain fruits, the highest concentrations of cyanidin are found in the seeds and skin. Cyanidin has been found to be a potent sirtuin 6 (SIRT6) activator.
Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.
Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a natural flavonol, a type of flavonoid, found in a variety of plants and plant-derived foods including kale, beans, tea, spinach, and broccoli. Kaempferol is a yellow crystalline solid with a melting point of 276–278 °C (529–532 °F). It is slightly soluble in water and highly soluble in hot ethanol, ethers, and DMSO. Kaempferol is named for 17th-century German naturalist Engelbert Kaempfer.
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.
Cryptophycins are a family of macrolide molecules that are potent cytotoxins and have been studied for potential antiproliferative properties useful in developing chemotherapy. They are members of the depsipeptide family.
The shikimate pathway is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids. This pathway is not found in animal cells.
Efrapeptins are peptides produced by fungi in the genus Tolypocladium that have antifungal, insecticidal, and mitochondrial ATPase inhibitory activities. They are produced via a biosynthetic pathway similar to but simpler than the Ciclosporin pathway, with nonribosomal peptide synthase (NRPS) and/or polyketide synthase (PKS) being the key elements.
Fungal isolates have been researched for decades. Because fungi often exist in thin mycelial monolayers, with no protective shell, immune system, and limited mobility, they have developed the ability to synthesize a variety of unusual compounds for survival. Researchers have discovered fungal isolates with anticancer, antimicrobial, immunomodulatory, and other bio-active properties. The first statins, β-Lactam antibiotics, as well as a few important antifungals, were discovered in fungi.
Medicinal fungi are fungi which contain metabolites or can be induced to produce metabolites through biotechnology to develop prescription drugs. Compounds successfully developed into drugs or under research include antibiotics, anti-cancer drugs, cholesterol and ergosterol synthesis inhibitors, psychotropic drugs, immunosuppressants and fungicides.
Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin. In 2006, the Nicolaou group discovered atrop-abyssomicin C while working on the total synthesis of abyssomicin C. Then in 2007, Süssmuth and co-workers isolated atrop-abyssomicin C from Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB, thereby depleting the biosynthesis of p-aminobenzoate.
7β-Hydroxyepiandrosterone (7β-OH-EPIA), also known as 5α-androstan-3β,7β-diol-17-one, is an endogenous androgen, estrogen, and neurosteroid that is produced from dehydroepiandrosterone and epiandrosterone. It has neuroprotective effects and, along with 7α-hydroxyepiandrosterone, may mediate the neuroprotective effects of DHEA. 7β-OH-EPIA may act as a highly potent antagonist of the G protein-coupled estrogen receptor (GPER).
The OU Citizen Science Soil Collection Program is a University of Oklahoma crowdsourcing program collecting and examining soil samples for fungi that might contain anticancer activity.
Swinholides are dimeric 42 carbon-ring polyketides that exhibit a 2-fold axis of symmetry. Found mostly in the marine sponge Theonella, swinholides encompass cytotoxic and antifungal activities via disruption of the actin skeleton. Swinholides were first described in 1985 and the structure and stereochemistry were updated in 1989 and 1990, respectively. Thirteen swinholides have been described in the literature, including close structural compounds such as misakinolides/bistheonellides, ankaraholides, and hurgholide A It is suspected that symbiotic microbes that inhabit the sponges rather than the sponges themselves produce swinholides since the highest concentration of swinholides are found in the unicellular bacterial fraction of sponges and not in the sponge fraction or cyanobacteria fraction that also inhabit the sponges.
Dihydromaltophilin, or heat stable anti-fungal factor (HSAF), is a secondary metabolite of Streptomyces sp. and Lysobacter enzymogenes. HSAF is a polycyclic tetramate lactam containing a single tetramic acid unit and a 5,5,6-tricyclic system. HSAF has been shown to have anti-fungal activity mediated through the disruption of the biosynthesis of Sphingolipid's by targeting a ceramide synthase unique to fungi.
