 | |
| Names | |
|---|---|
| IUPAC name (4aR,5S,12bS)-11-Bromo-8,10-dihydroxy-2,5-dimethyl-5-(4-methylpent-3-enyl)-3,4,4a,12b-tetrahydronaphtho[2,3-c]isochromene-7,12-dione | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider | |
PubChem CID | |
| |
| |
| Properties | |
| C25H27BrO5 | |
| Molar mass | 487.390 g·mol−1 |
| Related compounds | |
Related compounds | Debromomarinone |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Marinone is an antibiotic made by marine actinomycetes. [1]
The proposed biosynthesis of marinone was first reported by Murray et al. in 2018. [2] The biosynthesis of marinone begins with 1,3,6,8-tetrahydroxynaphthalene (THN), which is known to be biosynthesized via the condensation of five malonyl-coenzyme A units followed by the aromatization of the resulting pentaketide using a type III polyketide synthase. [3] Next, THN undergoes geranylation or farnesylation at the C-4 position, yielding 1 (Fig. 1). This transformation is catalyzed in vivo by NphB aromatic prenyltransferase in naphterpin biosynthesis [4] or by CnqP3 or CnqP4 in marinone biosynthesis. [5] Then, 1 undergoes oxidative dearomatization which is catalyzed by VCPO, which is a vanadium-dependent chloroperoxidase enzyme. This transformation yields compound 2. Compound 2 then undergoes two consecutive chlorinations at the C2 position, catalyzed by VCPO, to yield 4. Next, a VCPO catalyzed α-hydroxyketone rearrangement shifts the geranyl substituent from C-4 to C-3, yielding 5. Exposure of 5 to mildly basic conditions induces cyclization to yield the α-chloroepoxide, 6. This is followed by the reductive halogenation of the α-chloroepoxide to yield the hydroxynaphthoquinone, 7. Next, oxidation at the C-2 position and facile E/Z isomerization of the double bond affords the enone, 8, which undergoes a intramolecular hetero-Diels-Alder to yield debromomarinone. Lastly, the vanadium-dependent bromoperoxidase catalyzes the bromination of debromomarinone at the C-5 position to result in the formation of marinone.
Oxytetracycline is a broad-spectrum tetracycline antibiotic, the second of the group to be discovered.
In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups: [−C(=O)−CH2−]n. 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.
In molecular biology, biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms.
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.
The mitomycins are a family of aziridine-containing natural products isolated from Streptomyces caespitosus or Streptomyces lavendulae. They include mitomycin A, mitomycin B, and mitomycin C. When the name mitomycin occurs alone, it usually refers to mitomycin C, its international nonproprietary name. Mitomycin C is used as a medicine for treating various disorders associated with the growth and spread of cells.
'Novobiocin, also known as albamycin or ', is an aminocoumarin antibiotic that is produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides a member of the class Actinomycetia. Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. Novobiocin was first reported in the mid-1950s.
Thienamycin is one of the most potent naturally produced antibiotics known thus far, discovered in Streptomyces cattleya in 1976. Thienamycin has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes. Thienamycin is a zwitterion at pH 7.
Doxorubicin (DXR) is a 14-hydroxylated version of daunorubicin, the immediate precursor of DXR in its biosynthetic pathway. Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of streptomyces. In contrast, only one known non-wild type species, streptomyces peucetius subspecies caesius ATCC 27952, was initially found to be capable of producing the more widely used doxorubicin. This strain was created by Arcamone et al. in 1969 by mutating a strain producing daunorubicin, but not DXR, at least in detectable quantities. Subsequently, Hutchinson's group showed that under special environmental conditions, or by the introduction of genetic modifications, other strains of streptomyces can produce doxorubicin. His group has also cloned many of the genes required for DXR production, although not all of them have been fully characterized. In 1996, Strohl's group discovered, isolated and characterized dox A, the gene encoding the enzyme that converts daunorubicin into DXR. By 1999, they produced recombinant Dox A, a Cytochrome P450 oxidase, and found that it catalyzes multiple steps in DXR biosynthesis, including steps leading to daunorubicin. This was significant because it became clear that all daunorubicin producing strains have the necessary genes to produce DXR, the much more therapeutically important of the two. Hutchinson's group went on to develop methods to improve the yield of DXR, from the fermentation process used in its commercial production, not only by introducing Dox A encoding plasmids, but also by introducing mutations to deactivate enzymes that shunt DXR precursors to less useful products, for example baumycin-like glycosides. Some triple mutants, that also over-expressed Dox A, were able to double the yield of DXR. This is of more than academic interest because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum. More efficient production techniques have brought the price down to $1.1 million per kg for the non-liposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively.
Indolocarbazoles (ICZs) are a class of compounds that are under current study due to their potential as anti-cancer drugs and the prospective number of derivatives and uses found from the basic backbone alone. First isolated in 1977, a wide range of structures and derivatives have been found or developed throughout the world. Due to the extensive number of structures available, this review will focus on the more important groups here while covering their occurrence, biological activity, biosynthesis, and laboratory synthesis.
Ergocryptine is an ergopeptine and one of the ergoline alkaloids. It is isolated from ergot or fermentation broth and it serves as starting material for the production of bromocriptine. Two isomers of ergocryptine exist, α-ergocryptine and β-ergocryptine. The beta differs from the alpha form only in the position of a single methyl group, which is a consequence of the biosynthesis in which the proteinogenic amino acid leucine is replaced by isoleucine. β-Ergocryptine was first identified in 1967 by Albert Hofmann. Ergot from different sources have different ratios of the two isomers.
Enediynes are organic compounds containing two triple bonds and one double bond.
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.
Geosmin synthase or germacradienol-geosmin synthase designates a class of bifunctional enzymes that catalyze the conversion of farnesyl diphosphate (FPP) to geosmin, a volatile organic compound known for its earthy smell. The N-terminal half of the protein catalyzes the conversion of farnesyl diphosphate to germacradienol and germacrene D, followed by the C-terminal-mediated conversion of germacradienol to geosmin. The conversion of FPP to geosmin was previously thought to involve multiple enzymes in a biosynthetic pathway.
Debromomarinone is a chemical compound isolated from marine actinomycetes.
Streptomyces isolates have yielded the majority of human, animal, and agricultural antibiotics, as well as a number of fundamental chemotherapy medicines. Streptomyces is the largest antibiotic-producing genus of Actinomycetota, producing chemotherapy, antibacterial, antifungal, antiparasitic drugs, and immunosuppressants. Streptomyces isolates are typically initiated with the aerial hyphal formation from the mycelium.
Nosiheptide is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus.
Enterocin and its derivatives are bacteriocins synthesized by the lactic acid bacteria, Enterococcus. This class of polyketide antibiotics are effective against foodborne pathogens including L. monocytogenes, Listeria, and Bacillus. Due to its proteolytic degradability in the gastrointestinal tract, enterocin is used for controlling foodborne pathogens via human consumption.
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.