Pyrimidine nucleosides, as intermediate materials of significant commercial value, find extensive applications in the pharmaceutical industry. However, the current production of pyrimidine nucleosides largely relies on chemical synthesis, creating environmental problems that do not align with sustainable development goals. Recent progress in systemic metabolic engineering and synthetic biology has enabled the synthesis of natural products like pyrimidine nucleosides through microbial fermentation, offering a more sustainable alternative. Nevertheless, the intricate and tightly regulated biosynthetic pathways involved in the microbial production of pyrimidine nucleosides pose a formidable challenge. This study focuses on metabolic engineering and synthetic biology strategies aimed at enhancing pyrimidine nucleoside production. These strategies include gene modification, transcriptional regulation, metabolic flux analysis, cofactor balance optimization, and transporter engineering. Finally, this research highlights the challenges involved in the further development of pyrimidine nucleoside-producing strains and offers potential solutions in order to provide theoretical guidance for future research endeavors in this field.

中文翻译：

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微生物系统代谢工程生产嘧啶核苷：理论分析研究与展望


嘧啶核苷作为具有重要商业价值的中间材料，在医药工业中有着广泛的应用。然而，目前嘧啶核苷的生产很大程度上依赖于化学合成，造成了与可持续发展目标不相符的环境问题。系统代谢工程和合成生物学的最新进展使得通过微生物发酵合成嘧啶核苷等天然产物成为可能，提供了一种更可持续的替代品。然而，微生物生产嘧啶核苷所涉及的复杂且严格调控的生物合成途径提出了巨大的挑战。本研究重点关注旨在提高嘧啶核苷产量的代谢工程和合成生物学策略。这些策略包括基因修饰、转录调控、代谢流分析、辅因子平衡优化和转运蛋白工程。最后，本研究强调了进一步开发嘧啶核苷生产菌株所面临的挑战，并提供了潜在的解决方案，以便为该领域的未来研究工作提供理论指导。