MetaCyc Enzyme: β-lactam synthetase

Gene: bls Accession Number: G-10269 (MetaCyc)

Synonyms: bls2, orf3

Species: Streptomyces clavuligerus

Recombinant β-lactam synthetase expressed in Escherichia coli has been purified. It was homogeneous by SDS-PAGE, although its experimentally detrmined molecular mass and subunit structure were not reported [Bachmann00]. The crystal structure of the enzyme has been reported [Miller01].

Gene Citations: [Jensen04, Bachmann98, Townsend02]

Molecular Weight of Polypeptide: 54.53 kD (from nucleotide sequence)

Unification Links: Protein Model Portal:P0DJQ7 , SMR:P0DJQ7 , UniProt:P0DJQ7

Relationship Links: Entrez-Nucleotide:RELATED-TO:U87786 , InterPro:IN-FAMILY:IPR000583 , InterPro:IN-FAMILY:IPR001962 , InterPro:IN-FAMILY:IPR014729 , InterPro:IN-FAMILY:IPR029055 , PDB:Structure:1jgt , PDB:Structure:1M1Z , PDB:Structure:1MB9 , PDB:Structure:1MBZ , PDB:Structure:1MC1 , Pfam:IN-FAMILY:PF00733 , Pfam:IN-FAMILY:PF13537

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Created 23-Oct-2007 by Fulcher CA , SRI International

Enzymatic reaction of: β-lactam synthetase

Synonyms: (carboxyethyl)arginine β-lactam synthase, β-LS

EC Number:

L-N2-(2-carboxyethyl)arginine + ATP <=> deoxyamidinoproclavaminate + AMP + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: clavulanate biosynthesis

β-Lactam synthetase converts the β-amino acid N2-(2-carboxyethyl)-L-arginine to the monocyclic β-lactam deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate). This ATP and Mg2+-dependent enzyme catalyzes the intramolecular closure of the β-lactam ring in deoxyamidinoproclavaminate. A catalytic mechanism involving adenylation of N2-(2-carboxyethyl)-L-arginine followed by closure of the β-lactam ring has been proposed [Bachmann00, Miller02].

Product inhibition of the enzyme was demonstrated. Deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate) and diphosphate showed competitive and noncompetitive inhibition respectively when N2-(2-carboxyethyl)-L-arginine was the variable substrate. Deoxyamidinoproclavaminate (deoxyguanidinoproclavaminate) and diphosphate showed noncompetitive and competitive inhibition respectively when ATP was the variable substrate [Bachmann00].

Inhibitors (Unknown Mechanism): deoxyamidinoproclavaminate [Bachmann00] , diphosphate [Bachmann00]


Bachmann00: Bachmann BO, Townsend CA (2000). "Kinetic mechanism of the beta-lactam synthetase of Streptomyces clavuligerus." Biochemistry 39(37);11187-93. PMID: 10985764

Bachmann98: Bachmann BO, Li R, Townsend CA (1998). "beta-Lactam synthetase: a new biosynthetic enzyme." Proc Natl Acad Sci U S A 95(16);9082-6. PMID: 9689037

Jensen04: Jensen SE, Paradkar AS, Mosher RH, Anders C, Beatty PH, Brumlik MJ, Griffin A, Barton B (2004). "Five additional genes are involved in clavulanic acid biosynthesis in Streptomyces clavuligerus." Antimicrob Agents Chemother 48(1);192-202. PMID: 14693539

Miller01: Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC (2001). "Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine." Nat Struct Biol 8(8);684-9. PMID: 11473258

Miller02: Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC (2002). "The catalytic cycle of beta -lactam synthetase observed by x-ray crystallographic snapshots." Proc Natl Acad Sci U S A 99(23);14752-7. PMID: 12409610

Tahlan04a: Tahlan K, Park HU, Wong A, Beatty PH, Jensen SE (2004). "Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in Streptomyces clavuligerus." Antimicrob Agents Chemother 48(3);930-9. PMID: 14982786

Townsend02: Townsend CA (2002). "New reactions in clavulanic acid biosynthesis." Curr Opin Chem Biol 6(5);583-9. PMID: 12413541

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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