Yes / 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. / Medical Research Council, Biotechnology and Biological Sciences Research Council (BB/L000121/1)
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/17011 |
| Date | 2016 December 1928 |
| Creators | Hamed, Refaat B., Henry, L., Claridge, T.D.W., Schofield, C. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | (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., Unspecified |
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