André Alain A M, Rehnberg Nikita, Garg Ankush, Kjærgaard Magnus
Department of Molecular Biology and Genetics, Aarhus University, Denmar.
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Denmark.
Adv Biol (Weinh). 2025 May;9(5):e2400672. doi: 10.1002/adbi.202400672. Epub 2025 Apr 7.
Biology uses membrane-less organelles or biomolecular condensates as dynamic reaction compartments that can form or dissolve to regulate biochemical pathways. This has led to a flurry of research aiming to design new synthetic organelles that function as reaction crucibles for enzymes and biomolecular cascades in biotechnology. The mechanisms by which a condensate can enhance multistep biochemical processes including mass action, tuning the chemical environment, scaffolding and metabolic channelling is reviewed. These mechanisms are not inherently beneficial for the rate of enzymatic processes but can also inhibit a reaction. Similarly, some aspects of condensates are likely intrinsically inhibitory including retardation of diffusion, where the net effect of a condensate will be a trade-off between inhibitory and stimulatory effects. It is discussed which generalizable conclusions can be drawn so far and how close it is to design principles for condensates for enzyme cascades in microbial cell factories including which reactions are likely to be enhanced by condensates and which type of condensate will be suited for which reaction.
生物学利用无膜细胞器或生物分子凝聚物作为动态反应隔室，这些隔室可以形成或溶解以调节生化途径。这引发了一系列研究，旨在设计新型合成细胞器，这些细胞器在生物技术中可作为酶和生物分子级联反应的反应坩埚。本文综述了凝聚物增强多步生化过程的机制，包括质量作用、调节化学环境、支架作用和代谢通道化。这些机制并非对酶促过程的速率固有地有益，也可能抑制反应。同样，凝聚物的某些方面可能本质上具有抑制作用，包括扩散延迟，凝聚物的净效应将是抑制作用和刺激作用之间的权衡。本文讨论了目前可以得出哪些可推广的结论，以及距离微生物细胞工厂中酶级联反应凝聚物的设计原则有多接近，包括哪些反应可能会被凝聚物增强，以及哪种类型的凝聚物适合哪种反应。
