Liu Lu, Wang Kai, Liu Pan, Ba Limin, Liu Huan, Liu Yanhui
State Key Laboratory of Green Biomanufacturing, National Energy R&D Center for Biorefinery, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Beijing Key Laboratory of Green Chemicals Biomanufacturing, Beijing Synthetic Bio-Manufacturing Technology Innovation Center, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Biology (Basel). 2025 Apr 25;14(5):469. doi: 10.3390/biology14050469.
Methylparaben (MP) is an important member of the paraben family of aromatic compounds, which is under great demand in the industrial market as an antibacterial agent, preservative, and feed additive, and also has potential application value in the preparation of bio-based polyetherester materials. However, the current chemical production method of MP has various problems, such as serious environmental pollution, its dependence on petrochemical resources, and the generation of different types of waste. It is of great significance to develop an environmentally friendly MP synthesis method via synthetic biology. In this work, was used as the host to construct the biosynthetic pathway of MP and various metabolic engineering strategies were applied to break the bottlenecks in the synthesis process, including the regulation of the rate-limiting steps in the endogenous shikimate pathway, the enhancement of central carbon flux via knocking out competitive pathways and promoting precursors synthesis, and the improvement of the exogenous enzyme expression using promoter engineering. The final engineered could produce 68.59 mg/L MP in shake flasks, which was the highest titer of MP synthesized by so far. It was indicated that the strategies applied in our work were effective in promoting the synthesis of MP, which not only laid an important foundation for the industrial production of MP, but also provided a platform for the synthesis of other aromatic compounds.
对羟基苯甲酸甲酯（MP）是芳香族化合物对羟基苯甲酸酯家族的重要成员，作为抗菌剂、防腐剂和饲料添加剂在工业市场上有很大需求，在生物基聚醚酯材料制备中也具有潜在应用价值。然而，目前MP的化学生产方法存在各种问题，如环境污染严重、依赖石化资源以及产生不同类型的废物。通过合成生物学开发一种环境友好的MP合成方法具有重要意义。在这项工作中，以[具体宿主]为宿主构建MP的生物合成途径，并应用各种代谢工程策略打破合成过程中的瓶颈，包括对内源莽草酸途径限速步骤的调控、通过敲除竞争途径和促进前体合成增强中心碳通量，以及利用启动子工程提高外源酶表达。最终构建的工程菌株在摇瓶中可产生68.59 mg/L的MP，这是迄今为止[具体宿主]合成MP的最高产量。结果表明，我们工作中应用的策略对促进MP的合成是有效的，这不仅为MP的工业化生产奠定了重要基础，也为其他芳香族化合物的合成提供了一个平台。
