sq-27860 and thienamycin

sq-27860 has been researched along with thienamycin* in 1 studies

Other Studies

1 other study(ies) available for sq-27860 and thienamycin

ArticleYear
Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carbapenem biosynthesis.
    The Journal of biological chemistry, 2004, Feb-20, Volume: 279, Issue:8

    Carboxymethylproline synthase (CarB) catalyzes the committed step in the biosynthesis of (R)-1-carbapen-2-em-3-carboxylate, the simplest member of the carbapenem family of beta-lactam antibiotics, some of which are used clinically. CarB displays sequence homology with members of the crotonase family including enoyl-CoA hydratase (crotonase) and methylmalonyl-CoA decarboxylase. The CarB reaction has been proposed to comprise condensation of acetyl coenzyme A (AcCoA) and glutamate semi-aldehyde to give (2S,5S)-carboxymethylproline ((2S,5S)-CMP). (2S,5S)-CMP is then cyclized in an ATP-driven reaction catalyzed by CarA to give a carbapenam, which is subsequently epimerized and desaturated to give a carbapenem in a CarC-mediated reaction. Here we report the purification of recombinant CarB and that it exists predominantly in a trimeric form as do other members of the crotonase family. AcCoA was not found to be a substrate for CarB. Instead malonyl-CoA was found to be a substrate, efficiently producing (2S,5S)-CMP in the presence of glutamate semi-aldehyde. In the absence of glutamate semi-aldehyde, mass spectrometric analysis indicated that CarB catalyzed the decarboxylation of malonyl-CoA to AcCoA. The reactions of CarB, CarA, and CarC were coupled in vitro demonstrating the viability of malonyl-CoA as a carbapenem precursor. CarB was also shown to accept methylmalonyl CoA as a substrate to form 6-methyl-(2S,5S)CMP, which in turn is a substrate for CarA. The implications of the results for the biosynthesis of both carbapenem-3-carboxylate and C-2/C-6-substituted carbapenems, such as thienamycin, are discussed.

    Topics: Acetyl Coenzyme A; Amino Acid Sequence; Carbapenems; Carbon; Carbon-Carbon Lyases; Chromatography, Gel; Circular Dichroism; Cloning, Molecular; Dithionitrobenzoic Acid; Electrophoresis, Polyacrylamide Gel; Enoyl-CoA Hydratase; Glutamates; Glutamic Acid; Kinetics; Lactams; Magnetic Resonance Spectroscopy; Malonyl Coenzyme A; Mass Spectrometry; Models, Chemical; Molecular Sequence Data; Pectobacterium; Protein Binding; Recombinant Proteins; Sequence Homology, Amino Acid; Stereoisomerism; Thienamycins

2004