Crotonase catalysis enables flexible production of functionalized prolines and carbapenams.

Journal article

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.

Authors: Hamed, R; Henry, L; Gomez-Castellanos, JR; Mecinović, J; Ducho, C

• Publication status: Published
• Journal: Journal of the American Chemical Society
• Volume: 134
• Issue: 1
• Pages: 471-479
• Publication date: 2012-01-01
• DOI: 10.1021/ja208318d
• EISSN: 1520-5126
• ISSN: 0002-7863
• Language: English
• Keywords: Protein Conformation; Methylation; Carbapenems; Models, Molecular; Carbon-Carbon Lyases; Biocatalysis; Protein Engineering; Proline