Genome Property Definition Page

AccessionGenProp0040
Namethiotemplate type non-ribosomal peptide biosynthesis
TypeSYSTEM
DescriptionNon-ribosomal peptides are an important class of natural product which are assembled by the sequential addition of units containing amino acid groups in peptide linkages. These natural products include antibiotics, siderophores, toxins and other compounds of biological and economic importance. These products are synthesized on large proteins called non-ribosomal peptide synthetases (NRPSs) which specify the amino acids to be added by the sequence of amino acid adenylation (activation) domains along the synthetase. NRPSs may utilize many more amino acids than the 20 to which the ribosomes are limited. In addition, NRPSs may form linkages between side-chain amino and carboxylate groups and may contain domains which catalyze epimerization, methylation, cross-linking, cyclization, oxidation, reduction and other modifications to the growing peptide chain. Chain initiation may incorporate fatty acids (in the case of lipodepsipeptides) or other non-amino acid, carboxylate-containing compounds and NRPSs may work in concert with polyketide synthetases to form hybrid peptide-ketide natural products. NRPSs, like type I polyketide synthetases, work via a thio-template mechanism in which the activated units are transferred to the thiol of bound pantetheine groups in a thio-ester linkage (of the amino acid carboxylates). Condensation domains then join two thioester-bound units to form a peptide bond. Release of the complete polypeptide chain may be via cyclization or through the action of a thioesterase or thioester reductase. Many of the constituent domains of NRPSs have been defined by HMM models. These include adenylation (AMP-binding enzyme, PF00501), condensation (PF00668), acyl/peptidyl carrier protein (thiolation, pantetheine-binding, PF00550), thioesterase (PF00975) and thioester reductase (TIGR01746) domains. In addition, the pantetheine binding domains are identified by a pair of PROSITE motifs (PS00012, PS50075). The minimal components of an NRPS are the C (condensation), A (adenylation) and T (thiolation) domains which are commonly organized into CAT modules. NRPSs are detected as genes which contain hits to all three of these domains. Genomes with at least one ORF which fulfills this condition will be assigned the YES state for this property. The value field will hold the number of ORFs found to be NRPSs. NRPSs may, however, be broken up into multiple genes at domain boundaries and thus the possibility exists of missing NRPS genes which are short and broken up into pieces having only two of the three essential domains. If the state NO has been set, this indicates that the genome has been manually reviewed.
Parent PropertyGenProp0077: natural products biosynthesis
Gene Ontology TermGO:0019184: nonribosomal peptide biosynthetic process (biological_process)

Components
Step NameStep NumRequiredEvidence (Method)Evidence Go Terms
condensation, adenylation and thiloation domains in a single ORFC+A+TYESC+A+T dom (RULES)
GO:0019184: nonribosomal peptide biosynthetic process

Parent Properties
AccessionName
GenProp0077natural products biosynthesis


Sibling Properties
AccessionName
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GenProp0967radical SAM maturase system, CXXX repeats type
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GenProp1029radical SAM/SPASM system SynChlorMet
GenProp1037radical SAM/SPASM system GRRM
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