The aminocyclitols are compounds related to cyclitols. They possess features of relative and absolute configuration that are characteristic of their class and have been extensively studied; but these features are not clearly displayed by general methods of stereochemical nomenclature, so that special methods of specifying their configuration are justified and have long been used. In other than stereochemical respects, their nomenclature should follow the general rules of organic chemistry. [1]
The aminocyclitol family of natural products is a class of sugar-derived microbial secondary metabolites that demonstrate significant biological activities. Aminocyclitols are found as a component of aminoglycoside antibiotics which is also called as pseudosugars or pseudosaccharides. Aminocyclitols have chemical structures of a carbon ring with amine functional group(s). The class of aminocyclitol containing natural products can be divided by ring sizes or types of precursors.
pactamycin
This class includes kanamycin, neomycin, gentamicin, apramycin, hygromycin.
This class includes streptomycin, spectinomycin.
This class includes acarbose, validamycin, validoxylamine A, [2] salbostatin, cetoniacytone A, [3] pyralomicin 1a, [4] kirkamide [5]
Sedoheptulose 7-phosphate, a pentose phosphate pathway intermediate, is a common precursor of C7N aminocyclitol moiety of natural products, such as acarbose, [6] validamycin A, [7] salbostatin, [8] cetoniacytone A, [9] [10] and pyralomicin 1a. [11] 2-epi-5-epi-valiolone synthase (EEVS), [6] [12] [13] one of the sugar phosphate cyclase family enzyme [9] and which is a homolog of 3-dehydroquinate synthase in shikimate pathway, catalyzes the formation of a common intermediate, 2-epi-5-epi-valiolone from sedoheptulose 7-phosphate. After multiple enzyme reaction steps, which include phosphorylation, [14] [15] epimerization, [16] dehydration, and keto-reduction reactions, valienol, an important core structure is formed which leads to the formation of C7N aminocyclitol containing natural products. In validamycin biosynthesis, the C-N linkage which connect the C7 cyclitol moiety to the other was found to be formed by unprecedented actions of nucleotidyltransferase [17] and glycosyltransferase-like enzymes [18] [19] [20] (which is termed pseudoglycosyltransferase).
Oxytetracycline is a broad-spectrum tetracycline antibiotic, the second of the group to be discovered.
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.
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 improved bioactivity.
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.
Viomycin is a member of the tuberactinomycin family, a group of nonribosomal peptide antibiotics exhibiting anti-tuberculosis activity. The tuberactinomycin family is an essential component in the drug cocktail currently used to fight infections of Mycobacterium tuberculosis. Viomycin was the first member of the tuberactinomycins to be isolated and identified, and was used to treat TB until it was replaced by the less toxic, but structurally related compound, capreomycin. The tuberactinomycins target bacterial ribosomes, binding RNA and disrupting bacterial protein synthesis and certain forms of RNA splicing. Viomycin is produced by the actinomycete Streptomyces puniceus.
Lincomycin is a lincosamide antibiotic that comes from the actinomycete Streptomyces lincolnensis. A related compound, clindamycin, is derived from lincomycin by using thionyl chloride to replace the 7-hydroxy group with a chlorine atom with inversion of chirality. It was released for medical use in September 1964.
Spectinomycin, sold under the tradename Trobicin among others, is an antibiotic useful for the treatment of gonorrhea infections. It is given by injection into a muscle.
The calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora, with calicheamicin γ1 being the most notable. It was isolated originally in the mid-1980s from the chalky soil, or "caliche pits", located in Kerrville, Texas. The sample was collected by a scientist working for Lederle Labs. It is extremely toxic to all cells and, in 2000, a CD33 antigen-targeted immunoconjugate N-acetyl dimethyl hydrazide calicheamicin was developed and marketed as targeted therapy against the non-solid tumor cancer acute myeloid leukemia (AML). A second calicheamicin-linked monoclonal antibody, inotuzumab ozogamicin an anti-CD22-directed antibody-drug conjugate, was approved by the U.S. Food and Drug Administration on August 17, 2017, for use in the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Calicheamicin γ1 and the related enediyne esperamicin are the two of the most potent antitumor agents known.
In enzymology, an inositol-3-phosphate synthase is an enzyme that catalyzes the chemical reaction
The enzyme aristolochene synthase catalyzes the chemical reaction
The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer Amycolatopsis mediterranei. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins.
Aucubin is an iridoid glycoside. Iridoids are commonly found in plants and function as defensive compounds. Iridoids decrease the growth rates of many generalist herbivores.
Nogalamycin is an anthracycline antibiotic produced by the soil bacteria Streptomyces nogalater. It has antitumor properties but it is also highly cardiotoxic. The less cardiotoxic semisynthetic analog menogaril was developed in the 1970s. Currently nogalamycin and menogaril are not used clinically.
Valienamine is a C-7 aminocyclitol found as a substructure of pseudooligosaccharides such as the antidiabetic drug acarbose and the antibiotic validamycin. It can be found in Actinoplanes species.
Pikromycin was studied by Brokmann and Hekel in 1951 and was the first antibiotic macrolide to be isolated. Pikromycin is synthesized through a type I polyketide synthase system in Streptomyces venezuelae, a species of Gram-positive bacterium in the genus Streptomyces. Pikromycin is derived from narbonolide, a 14-membered ring macrolide. Along with the narbonolide backbone, pikromycin includes a desosamine sugar and a hydroxyl group. Although Pikromycin is not a clinically useful antibiotic, it can be used as a raw material to synthesize antibiotic ketolide compounds such as ertythromycins and new epothilones.
Radical SAM is a designation for a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. rSAMs comprise the largest superfamily of metal-containing enzymes.
2'-N-acetylparomamine deacetylase (EC 3.5.1.112, btrD (gene), neoL (gene), kanN (gene)) is an enzyme with systematic name 2'-N-acetylparomamine hydrolase (acetate-forming). This enzyme catalyses the following chemical reaction
2-deoxy-scyllo-Inosose synthase is an enzyme with systematic name D-glucose-6-phosphate phosphate-lyase (2-deoxy-scyllo-inosose-forming). This enzyme catalyses the following chemical reaction
C-1027 or lidamycin is an antitumor antibiotic consisting of a complex of an enediyne chromophore and an apoprotein. It shows antibiotic activity against most Gram-positive bacteria. It is one of the most potent cytotoxic molecules known, due to its induction of a higher ratio of DNA double-strand breaks than single-strand breaks.
Cetoniacytone A is a secondary metabolite classified in the family of C7N aminocyclitols which include other natural products such as validamycin A, acarbose, and epoxyquinomicin. Cetoniacytone A was first identified from a culture of Actinomyces sp. (strain Lu 9419), an endosymbiotic Gram-positive bacillus found in the intestines of a rose chafer (Cetonia aureata). Preliminary feeding studies with [U-13C3]glycerol identified the core moiety, cetoniacytone, to be derived via the pentose phosphate pathway. Although agar plate diffusion assay studies of cetoniacytone A showed no antimicrobial activity against Gram-positive and Gram-negative bacteria, cetoniacytone A has demonstrated a significant growth inhibitory effect against human cancer cell lines including hepatocellular carcinoma (HEP G2) and breast adenocarcinoma (MCF 7).