Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes
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...
| Main Authors: | , , , |
|---|---|
| Format: | Journal article |
| Izdano: |
American Chemical Society
2016
|
| _version_ | 1826299744735985664 |
|---|---|
| author | Hamed, R Henry, L Claridge, T Schofield, C |
| author_facet | Hamed, R Henry, L Claridge, T Schofield, C |
| author_sort | Hamed, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:06:37Z |
| format | Journal article |
| id | oxford-uuid:da230e05-dd27-4b03-a73e-1d05e2d5fc8d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:06:37Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:da230e05-dd27-4b03-a73e-1d05e2d5fc8d2022-03-27T09:01:00ZStereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:da230e05-dd27-4b03-a73e-1d05e2d5fc8dSymplectic Elements at OxfordAmerican Chemical Society2016Hamed, RHenry, LClaridge, TSchofield, CStereoselective 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. |
| spellingShingle | Hamed, R Henry, L Claridge, T Schofield, C Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title | Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title_full | Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title_fullStr | Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title_full_unstemmed | Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title_short | Stereoselective production of dimethyl-substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| title_sort | stereoselective production of dimethyl substituted carbapenams via engineered carbapenem biosynthesis enzymes |
| work_keys_str_mv | AT hamedr stereoselectiveproductionofdimethylsubstitutedcarbapenamsviaengineeredcarbapenembiosynthesisenzymes AT henryl stereoselectiveproductionofdimethylsubstitutedcarbapenamsviaengineeredcarbapenembiosynthesisenzymes AT claridget stereoselectiveproductionofdimethylsubstitutedcarbapenamsviaengineeredcarbapenembiosynthesisenzymes AT schofieldc stereoselectiveproductionofdimethylsubstitutedcarbapenamsviaengineeredcarbapenembiosynthesisenzymes |