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| Main Authors: | , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Synthetic and systems biotechnology
2026
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/42179739/ |
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Table of Contents:
- Efficient whole-cell biocatalytic synthesis of 2'-deoxy-2'-fluoroadenosine, a key building block for nucleic acid drugs. Feng, Dandan Zhang, Tianshu Zhou, Guan Cao, Yanli Luo, Quan Xu, Huifang Lu, Xuefeng 2'-Deoxy-2'-fluoroadenosine (2'-F-dA) is a nucleoside analogue used as a key building block for oligonucleotide drugs. It can be biosynthesized from a low-cost 2'-deoxy-2'-fluorouridine via one-pot transglycosylation catalyzed by a thymidine phosphorylase (TP) and a purine nucleoside phosphorylase (PNP). However, reliance on purified enzymes and low space-time yields present challenges for industrial application of the process. Here, we develop a whole-cell-based biocatalytic system employing TP and PNP from , which demonstrates high catalytic efficiency and operational simplicity in scaled-up reaction. In particular, a thermal pretreatment of TP- and PNP-expressing whole cells, determined as 50 °C for 3 h, effectively suppressed endogenous deamination side reaction while enhancing 2'-F-dA yield. Subsequent optimization of enzyme and substrate loadings and their relative ratios achieved an unprecedented space-time yield of 1.22 g/L/h with 88.1 g/L product titer in a 500 mL scaled-up reaction, manifesting a highest total conversion of 68.2 %. An integrated purification process yielded gram-scale solid powder of 2'-F-dA with 98.0 % chemical purity and 85.0 % recovery. This novel whole-cell biocatalytic process demonstrates significant industrial potential for the production of 2'-F-dA.