Qin Nan, Zhu Fanghuan, Liu Yanyan, Liu Dehua, Chen Zhen
Key Laboratory of Industrial Biocatalysis (Ministry of Education), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
School of Physiology, Pharmacology & Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
ACS Synth Biol. 2024 Jan 19;13(1):351-357. doi: 10.1021/acssynbio.3c00606. Epub 2023 Dec 18.
1,2-Butanediol (1,2-BDO) is an important platform chemical widely utilized in the synthesis of polyester polyols, plasticizers, cosmetics, and pharmaceuticals. However, no natural metabolic pathway for its biosynthesis has been identified, and biological production of 1,2-BDO from renewable bioresources has not been reported so far. In this study, we designed and experimentally verified a feasible non-natural synthesis pathway for the production of 1,2-BDO from renewable carbohydrates for the first time. This pathway extends the l-threonine synthesis pathway by introducing two artificial metabolic modules to sequentially convert l-threonine into 2-hydroxybutyric acid and 1,2-BDO. Following key enzyme screening and enhancement of l-threonine synthesis module in the chassis microorganism, the best engineered strain was able to produce 0.15 g/L 1,2-BDO using glucose as the sole carbon source. This work lays the foundation for the bioproduction of 1,2-BDO from renewable resources.
1,2-丁二醇（1,2-BDO）是一种重要的平台化合物，广泛应用于聚酯多元醇、增塑剂、化妆品和药品的合成中。然而，尚未发现其生物合成的天然代谢途径，且目前尚无关于从可再生生物资源生物生产1,2-丁二醇的报道。在本研究中，我们首次设计并通过实验验证了一条可行的非天然合成途径，用于从可再生碳水化合物生产1,2-丁二醇。该途径通过引入两个人工代谢模块扩展了L-苏氨酸合成途径，将L-苏氨酸依次转化为2-羟基丁酸和1,2-丁二醇。在底盘微生物中进行关键酶筛选和L-苏氨酸合成模块强化后，最佳工程菌株能够以葡萄糖为唯一碳源生产0.15 g/L的1,2-丁二醇。这项工作为从可再生资源生物生产1,2-丁二醇奠定了基础。
