Zhou Xiao-Ling, Zhang Meng-Sang, Zheng Xing-Run, Zhang Zhi-Qian, Liu Jian-Zhong
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China.
Joint Research Center of Engineering Biologylogy Technology of Sun Yat-Sen University and Tidetron Bioworks, Guangzhou, 510275, China.
Adv Biotechnol (Singap). 2024 Apr 2;2(2):15. doi: 10.1007/s44307-024-00023-x.
Engineering microbial cell factories has been widely used to produce a variety of chemicals, including natural products, biofuels, and bulk chemicals. However, poor robustness limits microbial production on an industrial scale. Microbial robustness is essential to ensure reliable and sustainable production of targeted chemicals. In this study, we developed an approach to screen transcription factors to improve robustness using CRSPRa technology. We applied this approach to identify some transcription factors to increase the robustness of Escherichia coli to aromatic chemicals. Activation of hdfR, yldP, purR, sosS, ygeH, cueR, cra, and treR increased the robustness of E. coli to phenyllactic acid. Upregulation of some transcription factors also improved the robustness to caffeic acid (cra) or tyrosol (cra, cueR, treR, soxS, hdfR and purR). Our study demonstrated that transcription factor engineering using CRISPRa is a powerful method to increase microbial robustness. This research provides new approaches to efficiently find genes responsible for increasing microbial robustness.
工程化微生物细胞工厂已被广泛用于生产各种化学品,包括天然产物、生物燃料和大宗化学品。然而,较差的鲁棒性限制了微生物在工业规模上的生产。微生物鲁棒性对于确保目标化学品的可靠和可持续生产至关重要。在本研究中,我们开发了一种使用CRSPRa技术筛选转录因子以提高鲁棒性的方法。我们应用该方法鉴定了一些转录因子,以增强大肠杆菌对芳香族化学品的鲁棒性。激活hdfR、yldP、purR、sosS、ygeH、cueR、cra和treR可增强大肠杆菌对苯乳酸的鲁棒性。一些转录因子的上调也提高了对咖啡酸(cra)或酪醇(cra、cueR、treR、soxS、hdfR和purR)的鲁棒性。我们的研究表明,使用CRISPRa进行转录因子工程是提高微生物鲁棒性的有力方法。本研究为有效寻找负责提高微生物鲁棒性的基因提供了新方法。