A Chinese scientific research team published a latest article in Metabolic Engineering -- Using Escherichia coli as the chassis, they built a synthetic biology platform that can produce a variety of UMP (uridylic acid) derivatives, and successfully realized the important intermediate 5-methylmethacrylate for antiviral drugs. The production of methyluridine (5-MU), with the highest titer reaching 10.71g/L, paves the way for further transformation of E. coli as a cell factory for optimized production of 5-MU.

5-MU is an important intermediate for antiviral drugs such as zidovudine (CAS No.: 30516-87-1), stavudine(CAS No.: 3056-17-5) and alovudine(CAS No.: 25526-93-6), and is also the starting material for the synthesis of anti-tumor and antiviral drugs β-thymidine. Over the past few decades, its production has relied heavily on chemical and enzymatic strategies, using thymine and guanosine as initial substrates in the nucleoside phosphorylase-catalyzed synthesis of 5-MU, on enzymes and suitable reaction conditions. High requirements and high cost limit the production of 5-MU. However, in recent years, the functional discovery of key genes has led to the biosynthesis of 5-methyluridine (5-MU).

After years of hard work, Chinese researchers started by creating an artificial synthetic pathway for 5-methyluridine, using systems metabolic engineering and synthetic biology strategies to combine degradation pathway interruption, transcriptional level regulation, precursor supply enhancement, and targeted screening of synthetic genes. Using rational methods, we established a general-purpose and extensive E. coli synthetic biology platform for nucleoside pharmaceutical intermediates, and further developed an antibiotic-free fermentation strategy to achieve the production of 5-MU (with a potency of 10.71 g/L).

This achievement is expected to change the existing production model of nucleoside pharmaceutical intermediates and establish the cost advantage of industrial production. Therefore, it complies with China's national strategic needs for green and high-quality development and is a useful attempt to innovate traditional production processes.