The xenortides (A-D) are a class of linear peptides isolated from the bacterium Xenorhabdus nematophila , [1] [2] a symbiont of the entomopathogenic nematode Steinernema carpocapsae . This class of compounds is known for their insect virulence and cytotoxic biological activities. The tryptamide containing compounds (xenortides B and D) show higher biological activity than the phenylethylamides (xenortides A and C). The most biologically active compound was found to be xenortide B with a potency of less than 1.6 μM activity against Trypanosoma brucei rhodesiense (sleeping sickness) and Plasmodium falciparum (malaria), however it is also the most toxic to mammalian cells which limits its viability as a treatment. [1]
The biosynthesis of xenortides A-D consists of two non-ribosomal peptide synthases (NRPS) coded by genes XndA and XndB, as well as upstream NADH flavin reductase, and a D-aminopeptidase. The first NRPS (XndA) consists of a condensation, adenylation, methylation, and thiolation domain, and has been implicated for the loading of N-methylleucine (xenortides A-B) or N-methylvaline (xenortides C-D). The second NRPS (XndB) consists of a condensation, adenylation, methylation, thiolation, and terminal condensation domains. XndB has been implicated in elongation with N-methylphenylalanine, as well as the final condensation of the enzyme-bound peptide with either decarboxylated phenylalanine (xenortides A and C) or decarboxylated tryptophan (xenortides B and D), ending the biosynthesis. [1]
A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiologically important, and some are both physiologically and commercially significant. A well known dipeptide is aspartame, an artificial sweetener.
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a semisynthetic glycopeptide antibiotic with a spectrum of activity similar to vancomycin. Its mechanism of action is to inhibit bacterial cell wall synthesis.
Antimycins are produced as secondary metabolites by Streptomyces bacteria, a soil bacteria. These specialized metabolites likely function to kill neighboring organisms in order to provide the streptomyces bacteria with a competitive edge.
Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms. While there exist a wide range of peptides that are not synthesized by ribosomes, the term nonribosomal peptide typically refers to a very specific set of these as discussed in this article.
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.
Gramicidin S or Gramicidin Soviet is an antibiotic that is effective against some gram-positive and gram-negative bacteria as well as some fungi.
The epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epothilones have better efficacy and milder adverse effects than taxanes.
Tyrocidine is a mixture of cyclic decapeptides produced by the bacteria Bacillus brevis found in soil. It can be composed of 4 different amino acid sequences, giving tyrocidine A–D. Tyrocidine is the major constituent of tyrothricin, which also contains gramicidin. Tyrocidine was the first commercially available antibiotic, but has been found to be toxic toward human blood and reproductive cells. The function of tyrocidine within its host B. brevis is thought to be regulation of sporulation.
Prodigiosin is the red dyestuff produced by many strains of the bacterium Serratia marcescens, as well as other Gram-negative, gamma proteobacteria such as Vibrio psychroerythrus and Hahella chejuensis. It is responsible for the pink tint occasionally found in grime that accumulates on porcelain surfaces such as bathtubs, sinks, and toilet bowls. It is in the prodiginines family of compounds which are produced in some Gram-negative gamma proteobacteria, as well as select Gram-positive Actinobacteria. The name prodigiosin is derived from prodigious.
Didemnins are cyclic depsipeptide compounds isolated from a tunicate of the genus Trididemnum that were collected in the Caribbean Sea. They were first isolated in 1978 at the University of Illinois.
Psymberin, also known as irciniastatin A, is a cytotoxin derived from sea sponges. It was discovered by two independent research groups, one led by Dr. Phil Crews and one led by Dr. Jean Schmidt, in 2004. Psymberin was found to be highly bioactive as it showed LC50s at nanomolar concentrations against various types of tumors.
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.
Apratoxin A - is a cyanobacterial secondary metabolite, known as a potent cytotoxic marine natural product. It is a derivative of the Apratoxin family of cytotoxins. The mixed peptide-polyketide natural product comes from a polyketide synthase/non-ribosomal peptide synthase pathway (PKS/NRPS). This cytotoxin is known for inducing G1-phase cell cycle arrest and apoptosis. This natural product's activity has made it a popular target for developing anticancer derivatives.
Atromentin is a natural chemical compound found in Agaricomycetes fungi in the orders Agaricales and Thelephorales. It can also be prepared by laboratory synthesis. Chemically, it is a polyphenol and a benzoquinone.
Cereulide is a toxin produced by some strains of Bacillus cereus. It is a potent cytotoxin that destroys mitochondria. It also causes nausea and vomiting.
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.
Geodia barretti is a massive deep-sea sponge species found in the boreal waters of the North Atlantic Ocean, and is fairly common on the coasts of Norway and Sweden. It is a dominant species in boreal sponge grounds. Supported by morphology and molecular data, this species is classified in the family Geodiidae.
Xenorhabdus bovienii is a bacterium from the genus of Xenorhabdus which has been isolated from the nematode Steinernema bibionis, Steinernema krsussei, Steinernema affine, Steinernema carpocapsae, Steinernema feltiae, Steinernema intermedium, Steinernema jollieti and Steinernema weiseri. Xenorhabdus bovienii produces N-Butanoylpyrrothine, N-(3-Methylbutanoyl)pyrrothine and Xenocyloins.
Xenorhabdus szentirmaii is a bacterium from the genus of Xenorhabdus which has been isolated from the nematode Steinernema rarum in Argentina. Xenorhabdus szentirmaii produces szentiamide, xenematide, bicornutin A xenofuranone A and xenofuranone B.