Stereoselective Production of Dimethyl-Substituted Carbapenams via Engineered Carbapenem Biosynthesis Enzymes

Stereoselective Production of Dimethyl-Substituted Carbapenams via Engineered Carbapenem Biosynthesis Enzymes
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通过工程碳青霉烯生物合成酶立体选择性生产二甲基取代的碳青霉烯类

DOI:
10.1021/acscatal.6b02509
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发表时间:
2017
期刊:
影响因子:
12.9
通讯作者:
Hamed R
Hamed R
中科院分区:
化学1区
文献类型:
--
作者:
Hamed R

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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 center, 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 manifestly improved hydrolytic stability compared to the unsubstituted carbapenams. The results highlight the use of modified carbapenem biosynthesis enzymes for production of carbapenams with improved properties.
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