Carbapenems are one of the five groups of the beta-lactam family of antibiotics and are currently the most important in clinical use in their broad specificity and resistance to B-lactamase enzymes. They contain an unsaturated, five-carbon ring fused to the nitrogen and carbon of the four-carbon β-lactam ring and act well against both Gram-positive and Gram-negative bacteria. This pathway shows the synthesis of several carbapenems in the bacterium Streptomyces cattleya and this is apparent from the fact that carbapenems are produced by Streptomyces. The pathway begins with the conversion of L-glutamate-5-semialdehyde (from L-Glutamic acid) and its cyclized form 1-Pyrroline-5-carboxylic acid along with the co-substrate malonyl-CoA into 2S,5S)-5-carboxymethyl proline. This intermediate is then converted into ((3S,5S)-carbapenam-3-carboxylate via the enzyme putative beta-lactam synthetase which is then epimerized and desaturated by carbapenem synthase to form the main product of this pathway: (5R)-Carbapenem-3-carboxylate. Stemming from this product, carbapenem biosynthesis intermediates 1-6 act as intermediates which lead to the synthesis of several variations of compounds that belong to the carbapenem family: thienamycin, N-acetylthienamycin, MM 4550 (a member of the olivanic acids and is the major carbapenem produced by S. argenteolus). It must be noted that the lack of direct connections between compounds in this illustration of the pathway accounts for the hypotheticality of the gene products in the reactions that connect one intermediate to the next.

Carbapenem Biosynthesis References