Entry
Name
Carbapenem biosynthesis - Gordonia jinghuaiqii
Description
Carbapenems are broad-spectrum beta-lactam antibiotics, which are often considered as the antibiotics of last resort. A naturally occurring carbapenem, thienamycin, was first discovered in Streptomyces cattleya. This diagram shows how a simple carbapenem, carbapenem-3-carboxylate, is synthesized from malonyl-CoA and pyrroline-5-carboxylate [MD:
M00675 ]. For structurally complex carbapenems, such as thienamycin, olivanic acid, epi-thienamycin and carbapenems of the OA-6129 group, uncertainty remains about the mechanism and timing for the inversion of the C-5 carbapenam bridgehead, the desaturation of the C-2/C-3 bond and the attachment of the C-2 and C-6 side chains.
Class
Metabolism; Biosynthesis of other secondary metabolites
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Gordonia jinghuaiqii [GN:
gji ]
Gene
Compound
C01134 Pantetheine 4'-phosphate
C01165 L-Glutamate 5-semialdehyde
C03912 (S)-1-Pyrroline-5-carboxylate
C06669 (5R)-Carbapen-2-em-3-carboxylate
C17366 (2S,5S)-trans-Carboxymethylproline
C17367 (3S,5S)-Carbapenam-3-carboxylic acid
C20816 Deacetylepithienamycin F
Reference
Authors
Stapon A, Li R, Townsend CA
Title
Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline.
Journal
Reference
Authors
Sleeman MC, Smith P, Kellam B, Chhabra SR, Bycroft BW, Schofield CJ
Title
Biosynthesis of carbapenem antibiotics: new carbapenam substrates for carbapenem synthase (CarC).
Journal
Reference
Authors
Sleeman MC, Schofield CJ
Title
Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carbapenem biosynthesis.
Journal
Reference
Authors
Hamed RB, Batchelar ET, Mecinovic J, Claridge TD, Schofield CJ
Title
Evidence that thienamycin biosynthesis proceeds via C-5 epimerization: ThnE catalyzes the formation of (2S,5S)-trans-carboxymethylproline.
Journal
Reference
Authors
Bodner MJ, Li R, Phelan RM, Freeman MF, Moshos KA, Lloyd EP, Townsend CA
Title
Definition of the common and divergent steps in carbapenem beta-lactam antibiotic biosynthesis.
Journal
Reference
Authors
Derzelle S, Duchaud E, Kunst F, Danchin A, Bertin P
Title
Identification, characterization, and regulation of a cluster of genes involved in carbapenem biosynthesis in Photorhabdus luminescens.
Journal
Reference
Authors
Rodriguez M, Nunez LE, Brana AF, Mendez C, Salas JA, Blanco G
Title
Mutational analysis of the thienamycin biosynthetic gene cluster from Streptomyces cattleya.
Journal
Reference
Authors
Williamson JM, Inamine E, Wilson KE, Douglas AW, Liesch JM, Albers-Schonberg G
Title
Biosynthesis of the beta-lactam antibiotic, thienamycin, by Streptomyces cattleya.
Journal
J Biol Chem 260:4637-47 (1985)
Reference
Authors
Nunez LE, Mendez C, Brana AF, Blanco G, Salas JA
Title
The biosynthetic gene cluster for the beta-lactam carbapenem thienamycin in Streptomyces cattleya.
Journal
Reference
Authors
Bodner MJ, Phelan RM, Freeman MF, Li R, Townsend CA
Title
Non-heme iron oxygenases generate natural structural diversity in carbapenem antibiotics.
Journal
Reference
Authors
Freeman MF, Moshos KA, Bodner MJ, Li R, Townsend CA
Title
Four enzymes define the incorporation of coenzyme A in thienamycin biosynthesis.
Journal
Reference
Authors
Buller AR, Labonte JW, Freeman MF, Wright NT, Schildbach JF, Townsend CA
Title
Autoproteolytic activation of ThnT results in structural reorganization necessary for substrate binding and catalysis.
Journal
Reference
Authors
Li R, Lloyd EP, Moshos KA, Townsend CA
Title
Identification and characterization of the carbapenem MM 4550 and its gene cluster in Streptomyces argenteolus ATCC 11009.
Journal
Related pathway
gji00330 Arginine and proline metabolism
KO pathway
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