176036-37-6Relevant articles and documents
Thioester hydrolysis and C-C bond formation by carboxymethylproline synthase from the crotonase superfamily
Batchelar, Edward T.,Hamed, Refaat B.,Ducho, Christian,Claridge, Timothy D. W.,Edelmann, Mariola J.,Kessler, Benedikt,Schofield, Christopher J.
, p. 9322 - 9325 (2008)
(Chemical Equation Presented) Enzyme in action: Labeling studies and the finding that carboxymethylproline synthase catalyzes production of deuterated (2S,5S)-6,6′-dimethyl-trans-carboxymethylproline (3) from dimethylmalonyl-CoA (1) and labeled l-pyrroline-5-carboxylate (2) limit possible mechanisms of C-C bond formation and thioester hydrolysis. A key feature in the catalysis is that intermediates are stabilized by hydrogen bonds in the oxy-anion hole of the enzyme (dark curve in scheme).
Definition of the common and divergent steps in carbapenem β-lactam antibiotic biosynthesis
Bodner, Micah J.,Li, Rongfeng,Phelan, Ryan M.,Freeman, Michael F.,Moshos, Kristos A.,Lloyd, Evan P.,Townsend, Craig A.
experimental part, p. 2159 - 2165 (2012/05/20)
Approximately 50 naturally occurring carbapenem β-lactam antibiotics are known. All but one of these have been isolated from Streptomyces species and are disubstituted structural variants of a simple core that is synthesized by Pectobacterium carotovorum
Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis
Ducho, Christian,Hamed, Refaat B.,Batchelar, Edward T.,Sorensen, John L.,Odell, Barbara,Schofield, Christopher J.
supporting information; experimental part, p. 2770 - 2779 (2009/09/07)
l-Glutamate semialdehyde (l-GSA) is an intermediate in biosynthetic pathways including those leading to the carbapenem antibiotics. We describe studies on asymmetric deuteration or hydrogenation of appropriate didehydro-amino acid precursors for the stereoselective synthesis of C-2- and/or C-3-[2H]-labelled l-GSA suitable for use in mechanistic studies. Regioselective deuterium incorporation into the 5-position of l-GSA was achieved using a labelled form of the Schwartz reagent (Cp2Zr 2HCl). 4,4-Dideuterated and fully backbone deuterated l-GSAs were prepared. The application of the labelled l-GSA derivatives to biosynthetic studies was exemplified by the chemo-enzymatic preparation of selectively deuterated trans-carboxymethylprolines using two different carboxymethylproline synthases (CarB and ThnE), enzymes that catalyse early steps in the biosynthesis of two carbapenems: (5R)-carbapenem-3-carboxylate and thienamycin, respectively. The Royal Society of Chemistry 2009.
