Entry Name Carbapenem biosynthesis
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 metabolitesBRITE hierarchy
Pathway map Ortholog table Module M00675 Carbapenem-3-carboxylate biosynthesis, pyrroline-5-carboxylate + malonyl-CoA => carbapenem-3-carboxylate [PATH:map00332 ]
Other DBs 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 map00330 Arginine and proline metabolism
KO pathway
