Oxytetracycline is a broad-spectrum tetracycline antibiotic, the second of the group to be discovered.
Streptomyces is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of Streptomyces bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, and have very large genomes with high GC content. Found predominantly in soil and decaying vegetation, most streptomycetes produce spores, and are noted for their distinct "earthy" odor that results from production of a volatile metabolite, geosmin. Different strains of the same species may colonize very diverse environments.
Streptomyces clavuligerus is a species of Gram-positive bacterium notable for producing clavulanic acid.
An efflux pump is an active transporter in cells that moves out unwanted material. Efflux pumps are an important component in bacteria in their ability to remove antibiotics. The efflux could also be the movement of heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.
Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.
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.
Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA gyrase enzyme involved in the cell division in bacteria. They are derived from Streptomyces species, whose best-known representative – Streptomyces coelicolor – was completely sequenced in 2002. The aminocoumarin antibiotics include:
Zwittermicin A is an antibiotic that has been identified from the bacterium Bacillus cereus UW85. It is a molecule of interest to agricultural industry because it has the potential to suppress plant disease due to its broad spectrum activity against certain gram positive and gram negative prokaryotic micro-organisms. The molecule is also of interest from a metabolic perspective because it represents a new structural class of antibiotic and suggests a crossover between polyketide and non-ribosomal peptide biosynthetic pathways. Zwittermicin A is linear aminopolyol.
Enediynes are organic compounds containing two triple bonds and one double bond.
Perimycin, also known as aminomycin and fungimycin, is polyene antibiotic produced by Streptomyces coelicolor var. aminophilus. The compound exhibits antifungal properties.
Methylenomycin A is a cyclopentanone derived antibiotic produced by Streptomyces coelicolor A3(2) that is effective against both Gram-negative and Gram-positive bacteria. Methylenomycins are naturally produced in two variants: A and B.
Methylenomycin B is a cyclopentanone derived antibiotic produced by Streptomyces coelicolor A3(2) that is effective against both Gram-negative and Gram-positive bacteria. Methylenomycins are naturally produced in two variants: A and B.
In molecular biology, the polyketide synthesis cyclase family of proteins includes a number of cyclases involved in polyketide synthesis in a number of actinobacterial species.
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.
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.
Streptomyces albidoflavus is a bacterium species from the genus of Streptomyces which has been isolated from soil from Poland. Streptomyces albidoflavus produces dibutyl phthalate and streptothricins.
Streptomyces albofaciens is a bacterium species from the genus of Streptomyces which produces oxytetracycline, spiramycin, albopeptin A, albopeptin B and alpomycin.
Cytochrome P450, family 105, also known as CYP105, is a cytochrome P450 monooxygenase family in bacteria, predominantly found in the phylum Actinomycetota and the order Actinomycetales. The first three genes and subfamilies identified in this family is the herbicide-inducible P-450SU1 and P-450SU2 from Streptomyces griseolus and choP from Streptomyces sp's cholesterol oxidase promoter region.
Genome mining describes the exploitation of genomic information for the discovery of biosynthetic pathways of natural products and their possible interactions. It depends on computational technology and bioinformatics tools. The mining process relies on a huge amount of data accessible in genomic databases. By applying data mining algorithms, the data can be used to generate new knowledge in several areas of medicinal chemistry, such as discovering novel natural products.
Tetracenomycin C is an antitumor anthracycline-like antibiotic produced by Streptomyces glaucescens GLA.0. The pale-yellow antibiotic is active against some gram-positive bacteria, especially against streptomycetes. Gram-negative bacteria and fungi are not inhibited. In considering the differences of biological activity and the functional groups of the molecule, tetracenomycin C is not a member of the tetracycline or anthracyclinone group of antibiotics. Tetracenomycin C is notable for its broad activity against actinomycetes. As in other anthracycline antibiotics, the framework is synthesized by a polyketide synthase and subsequently modified by other enzymes.
