KEGG   PATHWAY: ec00261
Entry
ec00261                     Pathway                                

Name
Monobactam biosynthesis
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
ec00261  Monobactam biosynthesis
ec00261

Module
M00736  Nocardicin A biosynthesis, L-pHPG + arginine + serine => nocardicin A [PATH:ec00261]
Enzyme
1.1.3.46   
1.13.11.46   
1.17.1.8   
1.2.1.11   
2.5.1.38   
2.6.1.103   
2.7.2.4   
2.7.7.4   
4.3.3.7   
5.1.1.14   
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
ec00250  Alanine, aspartate and glutamate metabolism
ec00260  Glycine, serine and threonine metabolism
ec00300  Lysine biosynthesis
ec00400  Phenylalanine, tyrosine and tryptophan biosynthesis
KO pathway
ko00261   
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