Biochemical retrosynthesis of 2-deoxyribonucleosides from glucose, acetaldehyde, and a nucleobase
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- 作者：Nobuyuki Horinouchi ; Jun Ogawa ; Takako Kawano ; Takafumi Sakai ; Kyota Saito ; Seiichiro Matsumoto ; Mie Sasaki ; Yoichi Mikami and Sakayu Shimizu
- 关键词：Deoxyribonucleoside ; Deoxyriboaldolase ; Glycolysis ; Phosphopentomutase ; Nucleoside phosphorylase ; nucleoside
- 刊名：Applied Microbiology and Biotechnology
- 出版年：2006
- 出版时间：August, 2006
- 年：2006
- 卷：71
- 期：5
- 页码：615-621
- 全文大小：140 KB
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Chemistry
Biotechnology
Microbiology
Microbial Genetics and Genomics - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0614
文摘
2′-Deoxyribonucleosides are important as building blocks for the synthesis of antisense drugs, antiviral nucleosides, and 2′-deoxyribonucleotides for polymerase chain reaction. The microbial production of 2′-deoxyribonucleosides from simple materials, glucose, acetaldehyde, and a nucleobase, through the reverse reactions of 2′-deoxyribonucleoside degradation and the glycolytic pathway, was investigated. The glycolytic pathway of baker’s yeast yielded fructose 1,6-diphosphate from glucose using the energy of adenosine 5′-triphosphate generated from adenosine 5′-monophosphate through alcoholic fermentation with the yeast. Fructose 1,6-diphosphate was further transformed to 2-deoxyribose 5-phosphate in the presence of acetaldehyde by deoxyriboaldolase-expressing Escherichia coli cells via d-glyceraldehyde 3-phosphate. E. coli transformants expressing phosphopentomutase and nucleoside phosphorylase produced 2′-deoxyribonucleosides from 2-deoxyribose 5-phosphate and a nucleobase via 2-deoxyribose 1-phosphate through the reverse reactions of 2′-deoxyribonucleoside degradation. Coupling of the glycolytic pathway and deoxyriboaldolase-catalyzing reaction efficiently supplied 2-deoxyribose 5-phosphate, which is a key intermediate for 2′-deoxyribonucleoside synthesis. 2′-Deoxyinosine (9.9 mM) was produced from glucose, acetaldehyde, and adenine through three-step reactions via fructose 1,6-diphosphate and then 2-deoxyribose 5-phosphate, the molar yield as to glucose being 17.8%.