The xenortides (A-D) are a class of linear peptides isolated from the bacterium '' Xenorhabdus nematophila'',{{Cite journal, last=Lang, first=Gerhard, last2=Kalvelage, first2=Tim, last3=Peters, first3=Arne, last4=Wiese, first4=Jutta, last5=Imhoff, first5=Johannes F., date=2008-06-01, title=Linear and Cyclic Peptides from the Entomopathogenic Bacterium Xenorhabdus nematophilus, journal=Journal of Natural Products, volume=71, issue=6, pages=1074–1077, doi=10.1021/np800053n, pmid=18491867, issn=0163-3864 a symbiont of the

entomopathogenic nematode Entomopathogenic nematodes (EPN) are a group of nematodes (thread worms), that cause death to insects. The term ''entomopathogenic'' has a Greek origin, with ''entomon'', meaning ''insect'', and ''pathogenic'', which means ''causing disease''. Th ...

Steinernema carpocapsae ''Steinernema carpocapsae'' is an entomopathogenic nematode and a member of the family Steinernematidae. It is a parasitic roundworm that has evolved an insect-killing symbiosis with bacteria, and kills its hosts within a few days of infection ...

''. 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 African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...

) and '' Plasmodium falciparum'' (

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

), however it is also the most toxic to mammalian cells which limits its viability as a treatment. The biosynthesis of xenortides A-D consists of two

non-ribosomal peptide 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 bacter ...

synthases (NRPS) coded by genes XndA and XndB, as well as upstream NADH flavin reductase, and a D-

aminopeptidase Aminopeptidases are enzymes that catalyze the cleavage of amino acids from the amino terminus ( N-terminus) of proteins or peptides (exopeptidases). They are widely distributed throughout the animal and plant kingdoms and are found in many subcel ...

. The first NRPS (XndA) consists of a condensation, adenylation, methylation, and

thiolation In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...

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 Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

(xenortides B and D), ending the biosynthesis. Xenortide_Biosynthesis

References

Dipeptides