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Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes
Hamed, Refaat B. Henry, L. Claridge, T.D.W. Schofield, C.
Hamed, Refaat B.
Henry, L.
Claridge, T.D.W.
Schofield, C.
Publication Date
28/12/2016
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(c) 2016 ACS. This is the author accepted manuscript following peer-review version of the article. The final version is available online from ACS at https://doi.org/10.1021/acscatal.6b02509.
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openAccess
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28/12/2016
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Abstract
Stereoselective biocatalysis by crotonase superfamily enzymes is exemplified by use of engineered 5-carboxymethylproline synthases (CMPSs) for preparation of functionalized 5-carboxymethylproline (5-CMP) derivatives methylated at two positions (i.e. C2/C6, C3/C6 and C5/C6), including products with a quaternary centre, from appropriately-substituted-amino acid aldehydes and C-2 epimeric methylmalonyl-CoA. The enzymatically-produced disubstituted 5-CMPs were converted by carbapenam synthetase into methylated bicyclic Β-lactams, which manifest improved hydrolytic stability compared to the unsubstituted carbapenams. The results highlight the use of modi-fied carbapenem biosynthesis enzymes for production of new carbapenams with improved properties.
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Accepted manuscript
Citation
Hamed RB, Henry L, Claridge TDW et al (2016) Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes. ACS Catalysis. 7(2): 1279-1285.
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Article