کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6489999 1416546 2018 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
New nucleoside hydrolase with transribosylation activity from Agromyces sp. MM-1 and its application for enzymatic synthesis of 2′-O-methylribonucleosides
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
New nucleoside hydrolase with transribosylation activity from Agromyces sp. MM-1 and its application for enzymatic synthesis of 2′-O-methylribonucleosides
چکیده انگلیسی
Microorganisms were screened for transribosylation activity between 2′-O-methyluridine (2′-OMe-UR) and nucleobases, for the purpose of developing a biotransformation process to synthesize 2′-O-methylribonucleosides (2′-OMe-NRs), which are raw materials for nucleic acid drugs. An actinomycete, Agromyces sp. MM-1 was found to produce 2′-O-methyladenosine (2′-OMe-AR) when whole cells were used in a reaction mixture containing 2′-OMe-UR and adenine. The enzyme responsible for the transribosylation was partially purified from Agromyces sp. MM-1 cells through a six-step separation procedure, and identified as a nucleoside hydrolase family enzyme termed AgNH. AgNH was a bi-functional enzyme catalyzing both hydrolysis towards 2′-OMe-NRs and transribosylation between 2′-OMe-UR and various nucleobases as well as adenine. In the hydrolysis reaction, AgNH preferred guanosine analogues as its substrates. In the transribosylation reaction, AgNH showed strong activity towards 6-chloroguanine, with 25-fold relative activity when adenine was used as the acceptor substrate. The transribosylation reaction product from 2′-OMe-UR and 6-chloroguanine was determined to 2′-O-methyl-6-chloroguanosine (2′-OMe-6ClGR). Under the optimal conditions, the maximum molar yield of 2′-OMe-6ClGR reached 2.3% in a 293-h reaction, corresponding to 440 mg/L.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Bioscience and Bioengineering - Volume 125, Issue 1, January 2018, Pages 38-45
نویسندگان
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