Kang Wei, Ma Xiao, Kakarla Deepika, Zhang Huawei, Fang Yunming, Chen Baizhu, Zhu Kongfu, Zheng Danni, Wu Zhiyue, Li Bo, Xue Chuang
State Key Laboratory of Fine Chemicals, Frontiers Science Centre for Smart Materials Oriented Chemical Engineering, School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.
Ningbo Institute of Dalian University of Technology, Ningbo, 315016, China.
Angew Chem Int Ed Engl. 2022 Dec 23;61(52):e202214001. doi: 10.1002/anie.202214001. Epub 2022 Nov 23.
Cells use self-assembled biomaterials such as lipid membranes or proteinaceous shells to coordinate thousands of reactions that simultaneously take place within crowded spaces. However, mimicking such spatial organization for synthetic applications in engineered systems remains a challenge, resulting in inferior catalytic efficiency. In this work, we show that protein cages as an ideal scaffold to organize enzymes to enhance cascade reactions both in vitro and in living cells. We demonstrate that not only enzyme-enzyme distance but also the improved K value contribute to the enhanced reaction rate of cascade reactions. Three sequential enzymes for lycopene biosynthesis have been co-localized on the exterior of the engineered protein cages in Escherichia coli, leading to an 8.5-fold increase of lycopene production by streamlining metabolic flux towards its biosynthesis. This versatile system offers a powerful tool to achieve enzyme spatial organization for broad applications in biocatalysis.
细胞利用自组装生物材料，如脂质膜或蛋白质外壳，来协调在拥挤空间内同时发生的数千种反应。然而，在工程系统中模拟这种空间组织以用于合成应用仍然是一个挑战，导致催化效率较低。在这项工作中，我们表明蛋白质笼作为一种理想的支架，可用于组织酶以增强体外和活细胞中的级联反应。我们证明，不仅酶与酶之间的距离，而且改善的K值都有助于提高级联反应的速率。用于番茄红素生物合成的三种连续酶已共定位在工程化蛋白质笼的外部，通过优化其生物合成的代谢通量，使番茄红素产量提高了8.5倍。这种多功能系统提供了一个强大的工具，可实现酶的空间组织，在生物催化中具有广泛的应用。
