کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11263471 | 1701130 | 2019 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enzymatic synthesis of sitagliptin intermediate using a novel Ï-transaminase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Enantiopure β-amino acids are essential precursors of various pharmaceuticals, agrochemicals and other industrially important chemicals. In this study, we selected sixteen potential Ï-Transaminases (Ï-TAs) by BLAST and phylogenetic tree analysis. These Ï-TAs were cloned, purified and tested for their reactivity for the synthesis of model β-amino acid (R)-3-amino-4-(2,4,5-triflurophenyl) butanoic acid [3-ATfBA], a key precursor for sitagliptin. In an enzymatic cascade, lipase converted β-ketoester substrate to β-keto acid, which was subsequently aminated by the selected Ï-TA to its corresponding β-amino acid. A potent enzyme from Ilumatobacter coccineus (Ï-TAIC) was identified for the production of 3-ATfBA. The pH dependency of the product inhibition suggested that lowering the reaction pH to 7.0 can circumvent the inhibition of Ï-TAIC by 3-ATfBA and about 92.3% conversion of 100âmM β-keto ester substrate could be achieved. The applicability of this enzymatic system was further evaluated at the scale of 140âmM, wherein 3-ATfBA was generated with excellent conversion (81.9%) and enantioselectivity (99% ee). Furthermore, Ï-TAIC was successfully used for the synthesis of various β-amino acids from their corresponding β-keto ester substrates.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Enzyme and Microbial Technology - Volume 120, January 2019, Pages 52-60
Journal: Enzyme and Microbial Technology - Volume 120, January 2019, Pages 52-60
نویسندگان
Geon-Hee Kim, Hyunwoo Jeon, Taresh P. Khobragade, Mahesh D. Patil, Sihyong Sung, Sanghan Yoon, Yumi Won, In Suk Choi, Hyungdon Yun,