KEGG PATHWAY: rn00261

PATHWAY: rn00261

Entry

rn00261                     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

rn00261

Monobactam biosynthesis

Module

M00736

Nocardicin A biosynthesis, L-pHPG + arginine + serine => nocardicin A [PATH:rn00261]

Reaction

R00480

ATP:L-aspartate 4-phosphotransferase

R00529

ATP:sulfate adenylyltransferase

R03072

S-adenosyl-L-methionine:nocardicin-E 3-amino-3-carboxypropyltransferase

R03073

nocardicin-A epimerase; isonocardicin-A epimerase

R04198

2,3,4,5-tetrahydrodipicolinate:NAD+ 4-oxidoreductase

R04199

2,3,4,5-tetrahydrodipicolinate:NADP+ 4-oxidoreductase

R04364

acetyl-CoA:L-2,3,4,5-tetrahydrodipicolinate N2-acetyltransferase

R06626

R06632

4-hydroxyphenylpyruvate:oxygen oxidoreductase (decarboxylating)

R06633

(S)-4-hydroxymandelate:oxygen 1-oxidoreductase

R10147

L-aspartate-4-semialdehyde hydro-lyase [adding pyruvate and cyclizing; (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate-forming]

R10880

R10881

S-adenosyl-L-methionine:nocardicin-G 3-amino-3-carboxypropyltransferase

R10882

nocardicin C,reduced ferredoxin:O2 oxidoreductase (nocardicin A-forming)

R10883

nocardicin-C epimerase

R10884

R10885

R10886

R10887

R10888

R10889

R10890

R10891

R10892

tabtoxinine-beta-lactam:L-threonine ligase (ADP-forming)

R10893

acetyl-CoA:tabtoxinine-beta-lactam N-acetyltransferase

R10894

R10895

R10903

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

C20912

C20913

C20914

C20915

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

PMID:23135477

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

PMID:15271351

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

PMID:15252031

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

PMID:15629944

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

PMID:12105888

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

PMID:11137816

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

PMID:25624104

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

PMID:24531841

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

PMID:22365611

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

PMID:23330869

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

PMID:16506699

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

PMID:22994681

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

PMID:23770908

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

rn00250

Alanine, aspartate and glutamate metabolism

rn00260

Glycine, serine and threonine metabolism

rn00300

Lysine biosynthesis

rn00400

Phenylalanine, tyrosine and tryptophan biosynthesis

KO pathway

ko00261

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