Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, PR China.
Key Lab for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, PR China.
ACS Synth Biol. 2023 May 19;12(5):1378-1395. doi: 10.1021/acssynbio.2c00671. Epub 2023 Apr 21.
With the rapid development of synthetic biology, various kinds of microbial cell factories (MCFs) have been successfully constructed to produce high-value-added compounds. However, the complexity of metabolic regulation and pathway crosstalk always cause issues such as intermediate metabolite accumulation, byproduct generation, and metabolic burden in MCFs, resulting in low efficiencies and low yields of industrial biomanufacturing. Such issues could be solved by spatially rearranging the pathways using intracellular compartments. In this review, design strategies are summarized and discussed based on the types and characteristics of natural and artificial subcellular compartments. This review systematically presents information for the construction of efficient MCFs with intracellular compartments in terms of four aspects of design strategy goals: (1) improving local reactant concentration; (2) intercepting and isolating competing pathways; (3) providing specific reaction substances and environments; and (4) storing and accumulating products.
随着合成生物学的快速发展，各种微生物细胞工厂（MCFs）已经被成功构建，用于生产高附加值化合物。然而，代谢调控和途径串扰的复杂性常常导致 MCF 中中间代谢物积累、副产物生成和代谢负担等问题，从而导致工业生物制造的效率和产量低下。这些问题可以通过利用细胞内隔室来重新排列途径来解决。在这篇综述中，根据天然和人工亚细胞隔室的类型和特点，总结并讨论了设计策略。本综述从设计策略目标的四个方面，即（1）提高局部反应物浓度；（2）拦截和隔离竞争途径；（3）提供特定的反应物质和环境；以及（4）储存和积累产物，系统地介绍了利用细胞内隔室构建高效 MCF 的信息。
