The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Rapamycin is also a macrolide and was originally developed as an antifungal, but is now used as an immunosuppressant drug and is being investigated as a potential longevity therapeutic.
Puromycin is an antibiotic protein synthesis inhibitor which causes premature chain termination during translation.
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.
Anisomycin, also known as flagecidin, is an antibiotic produced by Streptomyces griseolus which inhibits eukaryotic protein synthesis. Partial inhibition of DNA synthesis occurs at anisomycin concentrations that effect 95% inhibition of protein synthesis. Anisomycin can activate stress-activated protein kinases, MAP kinase and other signal transduction pathways.
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.
The peptidyl transferase is an aminoacyltransferase as well as the primary enzymatic function of the ribosome, which forms peptide bonds between adjacent amino acids using tRNAs during the translation process of protein biosynthesis. The substrates for the peptidyl transferase reaction are two tRNA molecules, one bearing the growing peptide chain and the other bearing the amino acid that will be added to the chain. The peptidyl chain and the amino acids are attached to their respective tRNAs via ester bonds to the O atom at the CCA-3' ends of these tRNAs. Peptidyl transferase is an enzyme that catalyzes the addition of an amino acid residue in order to grow the polypeptide chain in protein synthesis. It is located in the large ribosomal subunit, where it catalyzes the peptide bond formation. It is composed entirely of RNA. The alignment between the CCA ends of the ribosome-bound peptidyl tRNA and aminoacyl tRNA in the peptidyl transferase center contribute to its ability to catalyze these reactions. This reaction occurs via nucleophilic displacement. The amino group of the aminoacyl tRNA attacks the terminal carboxyl group of the peptidyl tRNA. Peptidyl transferase activity is carried out by the ribosome. Peptidyl transferase activity is not mediated by any ribosomal proteins but by ribosomal RNA (rRNA), a ribozyme. Ribozymes are the only enzymes which are not made up of proteins, but ribonucleotides. All other enzymes are made up of proteins. This RNA relic is the most significant piece of evidence supporting the RNA World hypothesis.
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.
Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.
EF-Tu is a prokaryotic elongation factor responsible for catalyzing the binding of an aminoacyl-tRNA (aa-tRNA) to the ribosome. It is a G-protein, and facilitates the selection and binding of an aa-tRNA to the A-site of the ribosome. As a reflection of its crucial role in translation, EF-Tu is one of the most abundant and highly conserved proteins in prokaryotes. It is found in eukaryotic mitochondria as TUFM.
50S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosomal RNA and 23S ribosomal RNA.
The 23S rRNA is a 2,904 nucleotide long component of the large subunit (50S) of the bacterial/archean ribosome and makes up the peptidyl transferase center (PTC). The 23S rRNA is divided into six secondary structural domains titled I-VI, with the corresponding 5S rRNA being considered domain VII. The ribosomal peptidyl transferase activity resides in domain V of this rRNA, which is also the most common binding site for antibiotics that inhibit translation, making it a target for ribosomal engineering. A well-known member of this antibiotic class, chloramphenicol, acts by inhibiting peptide bond formation, with recent 3D-structural studies showing two different binding sites depending on the species of ribosome. Numerous mutations in domains of the 23S rRNA with Peptidyl transferase activity have resulted in antibiotic resistance. 23S rRNA genes typically have higher sequence variations, including insertions and/or deletions, compared to other rRNAs.
A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.
Sparsomycin is a compound, initially discovered as a metabolite of the bacterium Streptomyces sparsogenes, which binds to the 50S ribosomal subunit and inhibits protein synthesis through peptidyl transferase inhibition. As it binds to the 50S ribosomal subunit, it induces translocation on the 30S subunit. It is a nucleotide analogue. It was also formerly thought to be a possible anti-tumor agent, but interest in this drug was later discarded after it was discovered that it resulted in retinopathy and as a tool to study protein synthesis; it is not specific for bacterial ribosomes and so not usable as an antibiotic.
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.
Streptogramin B is a subgroup of the streptogramin antibiotics family. These natural products are cyclic hexa- or hepta depsipeptides produced by various members of the genus of bacteria Streptomyces. Many of the members of the streptogramins reported in the literature have the same structure and different names; for example, pristinamycin IA = vernamycin Bα = mikamycin B = osteogrycin B.
Pleuromutilin and its derivatives are antibacterial drugs that inhibit protein synthesis in bacteria by binding to the peptidyl transferase component of the 50S subunit of ribosomes.
Bottromycin is a macrocyclic peptide with antibiotic activity. It was first discovered in 1957 as a natural product isolated from Streptomyces bottropensis. It has been shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among other Gram-positive bacteria and mycoplasma. Bottromycin is structurally distinct from both vancomycin, a glycopeptide antibiotic, and methicillin, a beta-lactam antibiotic.
Streptomyces halstedii is a bacterium species from the genus of Streptomyces which has been isolated from deeper soil layers. Streptomyces halstedii produces magnamycin B, vicenistatin deltamycin A2, deltamycin A3, bafilomycin B1 and bafilomycin C1. Streptomyces halstedii also produces complex antifungal antibiotics like oligomycins and the antibiotics anisomycin and sinefungin.
Lactimidomycin is a glutarimide antibiotic derived from the bacteria Streptomyces amphibiosporus. It has antifungal, antiviral and anti-cancer properties, acting as a direct inhibitor of protein translation in ribosomes. Antiviral activity is seen against a variety of RNA viruses including flaviviruses such as dengue fever, Kunjin virus and Modoc virus, as well as vesicular stomatitis virus and poliovirus. As lactimidomycin is a natural product containing an unusual unsaturated 12-membered lactone ring, it has been the subject of numerous total synthesis approaches.
Danica Galonić Fujimori is a Serbian-American chemical biologist who is a professor at the University of California, San Francisco. Her research considers nucleic acid synthesis and tissue engineering. In the search for new therapeutics and vaccines, she has studied the interactions between ribosomes and SARS-CoV-2.
