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.
Bleomycin is a medication used to treat cancer. This includes Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, ovarian cancer, and cervical cancer among others. Typically used with other cancer medications, it can be given intravenously, by injection into a muscle or under the skin. It may also be administered inside the chest to help prevent the recurrence of a pleural effusion due to cancer; however talc is better for this.
Burkholderia is a genus of Pseudomonadota whose pathogenic members include the Burkholderia cepacia complex, which attacks humans and Burkholderia mallei, responsible for glanders, a disease that occurs mostly in horses and related animals; Burkholderia pseudomallei, causative agent of melioidosis; and Burkholderia cepacia, an important pathogen of pulmonary infections in people with cystic fibrosis (CF). Burkholderia species is also found in marine environments. S.I. Paul et al. (2021) isolated and characterized Burkholderia cepacia from marine sponges of the Saint Martin's Island of the Bay of Bengal, Bangladesh.
The rpoB gene encodes the β subunit of bacterial RNA polymerase and the homologous plastid-encoded RNA polymerase (PEP). It codes for 1342 amino acids in E. coli, making it the second-largest polypeptide in the bacterial cell. It is targeted by the rifamycin family of antibacterials, such as rifampin. Mutations in rpoB that confer resistance to rifamycins do so by altering the protein's drug-binding residues, thereby reducing affinity for these antibiotics.
Burkholderia cenocepacia is a Gram-negative, rod-shaped bacterium that is commonly found in soil and water environments and may also be associated with plants and animals, particularly as a human pathogen. It is one of over 20 species in the Burkholderia cepacia complex (Bcc) and is notable due to its virulence factors and inherent antibiotic resistance that render it a prominent opportunistic pathogen responsible for life-threatening, nosocomial infections in immunocompromised patients, such as those with cystic fibrosis or chronic granulomatous disease. The quorum sensing systems CepIR and CciIR regulate the formation of biofilms and the expression of virulence factors such as siderophores and proteases. Burkholderia cenocepacia may also cause disease in plants, such as in onions and bananas. Additionally, some strains serve as plant growth-promoting rhizobacteria.
Burkholderia gladioli is a species of aerobic gram-negative rod-shaped bacteria that causes disease in both humans and plants. It can also live in symbiosis with plants and fungi and is found in soil, water, the rhizosphere, and in many animals. It was formerly known as Pseudomonas marginata.
Streptogramin A is a group of antibiotics within the larger family of antibiotics known as streptogramins. They are synthesized by the bacteria Streptomyces virginiae. The streptogramin family of antibiotics consists of two distinct groups: group A antibiotics contain a 23-membered unsaturated ring with lactone and peptide bonds while group B antibiotics are depsipeptides. While structurally different, these two groups of antibiotics act synergistically, providing greater antibiotic activity than the combined activity of the separate components. These antibiotics have until recently been commercially manufactured as feed additives in agriculture, although today there is increased interest in their ability to combat antibiotic-resistant bacteria, particularly vancomycin-resistant bacteria.
Callystatin A is a polyketide natural product from the leptomycin family of secondary metabolites. It was first isolated in 1997 from the marine sponge Callyspongia truncata which was collected from the Goto Islands in the Nagasaki Prefecture of Japan by the Kobayashi group. Since then its absolute configuration has been elucidated and callystatin A was discovered to have anti-fungal and anti-tumor activities with extreme potency against the human epidermoid carcinoma KB cells (IG50 = 10 pg/ml) and the mouse lymphocytic leukemia Ll210 cells (IG50 = 20 pg/ml).
Leinamycin is an 18-membered macrolactam produced by several species of Streptomyces atroolivaceus. This macrolactam has also been shown to exhibit antitumor properties as well as antimicrobial properties against gram-positive and gram-negative bacteria. The presence of a spiro-fused 1,3-dioxo-1,2-dithiolane moiety was a unique structural property at the time of this compound's discovery and it plays an important role in leinamycin's antitumor and antibacterial properties due to its ability to inhibit DNA synthesis.
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.
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.
Fostriecin is a type I polyketide synthase (PKS) derived natural product, originally isolated from the soil bacterium Streptomyces pulveraceus. It belongs to a class of natural products which characteristically contain a phosphate ester, an α,β-unsaturated lactam and a conjugated linear diene or triene chain produced by Streptomyces. This class includes structurally related compounds cytostatin and phoslactomycin. Fostriecin is a known potent and selective inhibitor of protein serine/threonine phosphatases, as well as DNA topoisomerase II. Due to its activity against protein phosphatases PP2A and PP4 which play a vital role in cell growth, cell division, and signal transduction, fostriecin was looked into for its antitumor activity in vivo and showed in vitro activity against leukemia, lung cancer, breast cancer, and ovarian cancer. This activity is thought to be due to PP2A's assumed role in regulating apoptosis of cells by activating cytotoxic T-lymphocytes and natural killer cells involved in tumor surveillance, along with human immunodeficiency virus-1 (HIV-1) transcription and replication.
Borrelidin is an 18-membered polyketide macrolide derived from several Streptomyces species. First discovered in 1949 from Streptomyces rochei, Borrelidin shows antibacterial activity by acting as an inhibitor of threonyl-tRNA synthetase and features a nitrile moiety, a unique functionality in natural products., Borrelidin also exhibits potent angiogenesis inhibition, which was shown in a rat aorta matrix model. Other studies have been performed to show that low concentrations of borrelidin can suppress growth and induce apoptosis in malignant acute lymphoblastic leukemia cells. Borredlidin's antimalarial activity has also been shown in vitro and in vivo.
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.
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.
Conipyridoin E is a tetramic acid derivative produced by the fungus Coniochaeta cephalothecoides which was found on a Tibetan Plateau. This natural product has been shown to exhibit antibacterial and antifungal activity against a variety of bacteria, such as Staphylococcus aureus, methicillin-resistant Staphyloccusaureus, and Enterococcus faecalis with MIC50 values of around 0.97 μM. Isolation of a number of analogs of conipyridoin has been accomplished by Han et al. in order to discover novel antibiotic natural products to combat antibiotic resistance.
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.
Prescopranone is a key intermediate in the biosynthesis of scopranones. Prescopranone is the precursor to scopranone A, scopranone B, and scopranone C, which are produced by Streptomyces sp. BYK-11038.
Andrimid is an antibiotic natural product that is produced by the marine bacterium Vibrio coralliilyticus. Andrimid is an inhibitor of fatty acid biosynthesis by blocking the carboxyl transfer reaction of acetyl-CoA carboxylase (ACC).
Disorazol, a cyclic polyketide synthesized by the bacterium Sorangium cellulosum So ce12, was first detected and isolated in 1994. Its chemical structure consists of a macrocyclic ring and two oxazole rings. Disorazol A has been demonstrated to exhibit anti-fungi activities, but it was not active against yeasts. In addition, this substance demonstrates potent anti-cancer characteristics at exceptionally low picomolar levels by obstructing the mechanism of tubulin assembly and triggering the disruption of microtubules. As a result, these impacts lead to the initiation of cell apoptosis. However, disorazols cannot be directly used as drugs in the clinic due to its extremely high cytotoxicity and instability. Thus, chemical and biosynthetic synthesis pathways were designed to synthesize unnatural derivatives of disorazol in hope of reducing its cytotoxicity without decreasing its anti-cancer potency.
