945859-84-7Relevant academic research and scientific papers
Crotonase catalysis enables flexible production of functionalized prolines and carbapenams
Hamed, Refaat B.,Henry, Luc,Gomez-Castellanos, J. Ruben,Mecinovic, Jasmin,Ducho, Christian,Sorensen, John L.,Claridge, Timothy D. W.,Schofield, Christopher J.
, p. 471 - 479 (2012)
The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.
