Escherichia coli K-12 substr. MG1655 Protein Class: a non-ribosomal peptide synthase

Abbrev Name: non-ribosomal peptide synthase

The biosynthetic system for the production of a non-ribosomal peptide operates nucleic acid-free at the protein level. The specific condensation of amino acids and related carboxyl containing compounds is directed by protein templates, and each biosynthetic step generally requires a protein module. A minimal configuration consists of an adenylation domain for amino acid activation, a thiolation domain for transfer of activated intermediates, and a condensation domain.

Domains and modules are assembled at the gene level into gene clusters, which are translated into multifunctional proteins or multi-enzyme complexes, and post-translationally modified by addition of 4'-phosphopantetheine to the thiolation domain [Welker06].

Since a minimal module requires 3-3.5 kbp of genetic sequence, and since most non-ribosomal peptide synthetases (NRPSs) consist of several such modules, some NRPS genes are the largest known genes [Finking04].

a non-ribosomal peptide synthase compound structure

Child Classes: 3-hydroxyquinaldyl-D-cysteinyl-glycyl-[non-ribosomal peptide synthase] (0), a DdaD non-ribosomal peptide synthase (0), a gramicidin-S synthetase (0), a PchE non-ribosomal peptide synthase protein (0), a PchF non-ribosomal peptide synthase protein (0), a PhsA non-ribosomal peptide synthase (0), a PhsB non-ribosomal peptide synthase (0), a PhsC non-ribosomal peptide synthase (0), an N-3-(R,R)-epoxysuccinamoyl-(S)-2,3-diaminopropanoyl-[DdaD non-ribosomal peptide synthase] (0), an N-3-fumaramoyl-(S)-2,3-diaminopropanoyl-[DdaD non-ribosomal peptide synthase] (0), L-alanyl-[PhsB non-ribosomal peptide synthase] (0), N-acetyl demethylphosphinothricinyl-L-alanyl-L-alanyl-[PhsC non-ribosomal peptide synthase] (0), N-acetyl demethylphosphinothricinyl-L-alanyl-L-leucyl-[PhsC non-ribosomal peptide synthase] (0), N-acetyl demethylphosphinothricinyl-L-alanyl-[PhsB non-ribosomal peptide synthase] (0), N-acetyl demethylphosphinothricinyl-[PhsA non-ribosomal peptide synthase] (0), quinoxaline-2-carboxyl-D-seryl-L-alanyl-[non-ribosomal peptide synthase] (0)


SMILES: CC(C)(COP(=O)([O-])OCC(N[a non-ribosomal peptide synthase])C(=O)[a non-ribosomal peptide synthase])C(O)C(=O)NCCC(=O)NCCS

Gene-Reaction Schematic

Gene-Reaction Schematic

Instance reaction of [an acyl-carrier protein + coenzyme A → adenosine 3',5'-bisphosphate + a holo-[acyl-carrier protein] + H+] (
i1: [EntB aryl-carrier protein] + coenzyme A → a holo-[EntB isochorismatase/aryl-carrier protein] + adenosine 3',5'-bisphosphate + H+ (

Created 11-Sep-2008 by Caspi R, SRI International


Finking04: Finking R, Marahiel MA (2004). "Biosynthesis of nonribosomal peptides1." Annu Rev Microbiol 58;453-88. PMID: 15487945

Fischbach06a: Fischbach MA, Walsh CT (2006). "Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms." Chem Rev 106(8);3468-96. PMID: 16895337

Hollenhorst10: Hollenhorst MA, Bumpus SB, Matthews ML, Bollinger JM, Kelleher NL, Walsh CT (2010). "The nonribosomal peptide synthetase enzyme DdaD tethers N(β)-fumaramoyl-l-2,3-diaminopropionate for Fe(II)/α-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis." J Am Chem Soc 132(44);15773-81. PMID: 20945916

Lambalot96: Lambalot RH, Gehring AM, Flugel RS, Zuber P, LaCelle M, Marahiel MA, Reid R, Khosla C, Walsh CT (1996). "A new enzyme superfamily - the phosphopantetheinyl transferases." Chem Biol 1996;3(11);923-36. PMID: 8939709

Stachelhaus95: Stachelhaus T, Marahiel MA (1995). "Modular structure of peptide synthetases revealed by dissection of the multifunctional enzyme GrsA." J Biol Chem 270(11);6163-9. PMID: 7534306

Welker06: Welker M, von Dohren H (2006). "Cyanobacterial peptides - nature's own combinatorial biosynthesis." FEMS Microbiol Rev 30(4);530-63. PMID: 16774586

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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