KEGG   PATHWAY: ecj00261
Entry
ecj00261                    Pathway                                
Name
Monobactam biosynthesis - Escherichia coli K-12 W3110
Description
Monobactams are beta-lactam antibiotics containing a monocyclic beta-lactam nucleus, which is structurally different from penicillin and cephalosporin core structures with another fused ring. This diagram shows biosynthesis of nocardicin A, a naturally occurring monobactam, via the pentapeptide formed by condensation of L-4-hydroxyphenylglycine (L-pHPG), L-arginine and L-serine [MD:M00736]. Other naturally occurring monobactams are also shown but the biosynthetic pathway is not yet fully characterized. Sulfazecin and other 3-aminomonobactamic acid derivatives are derived from serine or threonine, and tabtoxinine-beta-lactam is a phytotoxin. Aztreonam, a synthetic monobactam originally isolated as SQ 26,180 from Chromobacterium violaceum, is the first clinically used monobactam.
Class
Metabolism; Biosynthesis of other secondary metabolites
Pathway map
ecj00261  Monobactam biosynthesis
ecj00261

Organism
Escherichia coli K-12 W3110 [GN:ecj]
Gene
JW2721  cysN; sulfate adenylyltransferase, subunit 1 [KO:K00956] [EC:2.7.7.4]
JW2722  cysD; sulfate adenylyltransferase, subunit 2 [KO:K00957] [EC:2.7.7.4]
JW3984  lysC; aspartokinase III [KO:K00928] [EC:2.7.2.4]
JW0001  thrA; fused aspartokinase I and homoserine dehydrogenase I [KO:K12524] [EC:2.7.2.4 1.1.1.3]
JW3911  metL; fused aspartokinase II and homoserine dehydrogenase II [KO:K12525] [EC:2.7.2.4 1.1.1.3]
JW3396  asd; aspartate-semialdehyde dehydrogenase, NAD(P)-binding [KO:K00133] [EC:1.2.1.11]
JW2463  dapA; dihydrodipicolinate synthase [KO:K01714] [EC:4.3.3.7]
JW0029  dapB; dihydrodipicolinate reductase [KO:K00215] [EC:1.17.1.8]
Compound
C00019  S-Adenosyl-L-methionine
C00022  Pyruvate
C00049  L-Aspartate
C00059  Sulfate
C00062  L-Arginine
C00065  L-Serine
C00082  L-Tyrosine
C00188  L-Threonine
C00224  Adenylyl sulfate
C00441  L-Aspartate 4-semialdehyde
C00927  Isonocardicin A
C01179  3-(4-Hydroxyphenyl)pyruvate
C01739  Nocardicin E
C01941  Nocardicin A
C03082  4-Phospho-L-aspartate
C03198  (S)-4-Hydroxymandelate
C03590  4-Hydroxyphenylglyoxylate
C03972  2,3,4,5-Tetrahydrodipicolinate
C05539  N-Acetyl-L-2-amino-6-oxopimelate
C12323  L-4-Hydroxyphenylglycine
C16842  SQ 26180
C17351  Nocardicin C
C17352  Isonocardicin C
C17355  Nocardicin G
C20258  (2S,4S)-4-Hydroxy-2,3,4,5-tetrahydrodipicolinate
C20911  C20911
C20912  C20912
C20913  C20913
C20914  C20914
C20915  C20915
C20916  C20916
C20917  Tabtoxin
C20918  Tabtoxinine-beta-lactam
C20919  Isotabtoxin
C20920  Tabtoxinine-delta-lactam
C20921  N1-Acetyl-tabtoxinine-beta-lactam
C20927  Sulfazecin
C20928  MM 42842
C20929  3alpha-Hydroxy-3-aminoacylmonobactamic acid
Reference
  Authors
Hamed RB, Gomez-Castellanos JR, Henry L, Ducho C, McDonough MA, Schofield CJ
  Title
The enzymes of beta-lactam biosynthesis.
  Journal
Nat Prod Rep 30:21-107 (2013)
DOI:10.1039/c2np20065a
Reference
  Authors
Gunsior M, Breazeale SD, Lind AJ, Ravel J, Janc JW, Townsend CA
  Title
The biosynthetic gene cluster for a monocyclic beta-lactam antibiotic, nocardicin A.
  Journal
Chem Biol 11:927-38 (2004)
DOI:10.1016/j.chembiol.2004.04.012
Reference
  Authors
Kelly WL, Townsend CA
  Title
Mutational analysis and characterization of nocardicin C-9' epimerase.
  Journal
J Biol Chem 279:38220-7 (2004)
DOI:10.1074/jbc.M405450200
Reference
  Authors
Kelly WL, Townsend CA
  Title
Mutational analysis of nocK and nocL in the nocardicin a producer Nocardia uniformis.
  Journal
J Bacteriol 187:739-46 (2005)
DOI:10.1128/JB.187.2.739-746.2005
Reference
PMID:9804844
  Authors
Reeve AM, Breazeale SD, Townsend CA
  Title
Purification, characterization, and cloning of an S-adenosylmethionine-dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis.
  Journal
J Biol Chem 273:30695-703 (1998)
DOI:10.1074/jbc.273.46.30695
Reference
  Authors
Kelly WL, Townsend CA
  Title
Role of the cytochrome P450 NocL in nocardicin A biosynthesis.
  Journal
J Am Chem Soc 124:8186-7 (2002)
DOI:10.1021/ja025926g
Reference
  Authors
Hubbard BK, Thomas MG, Walsh CT
  Title
Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics.
  Journal
Chem Biol 7:931-42 (2000)
DOI:10.1016/S1074-5521(00)00043-0
Reference
  Authors
Gaudelli NM, Long DH, Townsend CA
  Title
beta-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis.
  Journal
Nature 520:383-7 (2015)
DOI:10.1038/nature14100
Reference
  Authors
Gaudelli NM, Townsend CA
  Title
Epimerization and substrate gating by a TE domain in beta-lactam antibiotic biosynthesis.
  Journal
Nat Chem Biol 10:251-8 (2014)
DOI:10.1038/nchembio.1456
Reference
  Authors
Davidsen JM, Townsend CA
  Title
In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A.
  Journal
Chem Biol 19:297-306 (2012)
DOI:10.1016/j.chembiol.2011.10.020
Reference
  Authors
Davidsen JM, Bartley DM, Townsend CA
  Title
Non-ribosomal propeptide precursor in nocardicin A biosynthesis predicted from adenylation domain specificity dependent on the MbtH family protein NocI.
  Journal
J Am Chem Soc 135:1749-59 (2013)
DOI:10.1021/ja307710d
Reference
PMID:6805424
  Authors
O'Sullivan J, Gillum AM, Aklonis CA, Souser ML, Sykes RB
  Title
Biosynthesis of monobactam compounds: origin of the carbon atoms in the beta-lactam ring.
  Journal
Antimicrob Agents Chemother 21:558-64 (1982)
DOI:10.1128/AAC.21.4.558
Reference
PMID:6859838
  Authors
O'Sullivan J, Souser ML, Kao CC, Aklonis CA
  Title
Sulfur metabolism in the biosynthesis of monobactams.
  Journal
Antimicrob Agents Chemother 23:598-602 (1983)
DOI:10.1128/AAC.23.4.598
Reference
  Authors
Kinscherf TG, Willis DK
  Title
The biosynthetic gene cluster for the beta-lactam antibiotic tabtoxin in Pseudomonas syringae.
  Journal
J Antibiot (Tokyo) 58:817-21 (2005)
DOI:10.1038/ja.2005.109
Reference
  Authors
Wencewicz TA, Walsh CT
  Title
Pseudomonas syringae self-protection from tabtoxinine-beta-lactam by ligase TblF and acetylase Ttr.
  Journal
Biochemistry 51:7712-25 (2012)
DOI:10.1021/bi3011384
Reference
  Authors
Arai T, Arimura Y, Ishikura S, Kino K
  Title
L-amino acid ligase from Pseudomonas syringae producing tabtoxin can be used for enzymatic synthesis of various functional peptides.
  Journal
Appl Environ Microbiol 79:5023-9 (2013)
DOI:10.1128/AEM.01003-13
Reference
PMID:1515668
  Authors
Engst K, Shaw PD
  Title
Identification of a lysA-like gene required for tabtoxin biosynthesis and pathogenicity in Pseudomonas syringae pv. tabaci strain PTBR2.024.
  Journal
Mol Plant Microbe Interact 5:322-9 (1992)
DOI:10.1094/mpmi-5-322
Reference
PMID:8990304
  Authors
Liu L, Shaw PD
  Title
Characterization of dapB, a gene required by Pseudomonas syringae pv. tabaci BR2.024 for lysine and tabtoxinine-beta-lactam biosynthesis.
  Journal
J Bacteriol 179:507-13 (1997)
DOI:10.1128/JB.179.2.507-513.1997
Reference
PMID:9294453
  Authors
Liu L, Shaw PD
  Title
A possible role for acetylated intermediates in diaminopimelate and tabtoxinine-beta-lactam biosynthesis in Pseudomonas syringae pv. tabaci BR2.024.
  Journal
J Bacteriol 179:5922-7 (1997)
DOI:10.1128/JB.179.18.5922-5927.1997
Reference
PMID:2881927
  Authors
Unkefer CJ, London RE, Durbin RD, Uchytil TF, Langston-Unkefer PJ
  Title
The biosynthesis of tabtoxinine-beta-lactam. Use of specifically 13C-labeled glucose and 13C NMR spectroscopy to identify its biosynthetic precursors.
  Journal
J Biol Chem 262:4994-9 (1987)
Related
pathway
ecj00250  Alanine, aspartate and glutamate metabolism
ecj00260  Glycine, serine and threonine metabolism
ecj00300  Lysine biosynthesis
ecj00400  Phenylalanine, tyrosine and tryptophan biosynthesis
KO pathway
ko00261   
LinkDB

DBGET integrated database retrieval system