Villaverde Antonio, Carrió M Mar
Institut de Biotecnologia i de Biomedicina and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Biotechnol Lett. 2003 Sep;25(17):1385-95. doi: 10.1023/a:1025024104862.
Protein aggregation is an ordinary consequence of thermal stress. In recombinant bacteria, the over-expression of plasmid-encoded genes triggers transcription of heat-shock genes and other stress responses and often results in the aggregation of the encoded protein as inclusion bodies. The formation of these deposits represents a major obstacle for the production of biologically active polypeptides and restricts the spectrum of protein products being available for the industrial-biomedical market. Inclusion body formation was formerly considered to occur passively by the irretrievable deposition of partially-folded intermediates. Increasing evidence, however, indicates that protein aggregation in bacteria occurs as a reversible process deeply integrated in the cell mechanisms for coping with thermal stress, and that inclusion bodies are structurally dynamic structures. Inclusion body formation might actually be supported by the cellular machinery that when operated under specific stress conditions, transiently stores misfolded polypeptides until they could be further processed: either refolded or proteolysed. A better understanding of protein aggregation in cell physiology could allow not only inclusion body formation to be minimized more efficiently for a higher soluble yield, but also to comprehend in detail the intricacy of cell mechanisms committed to handling the misfolding danger.
蛋白质聚集是热应激的常见后果。在重组细菌中，质粒编码基因的过度表达会触发热休克基因的转录和其他应激反应，并且常常导致编码的蛋白质以包涵体的形式聚集。这些沉积物的形成是生产生物活性多肽的主要障碍，并且限制了工业生物医学市场上可用的蛋白质产品范围。包涵体形成以前被认为是部分折叠中间体不可挽回的沉积而被动发生的。然而，越来越多的证据表明，细菌中的蛋白质聚集是一个可逆过程，深深融入细胞应对热应激的机制中，并且包涵体是结构动态的结构。包涵体的形成实际上可能得到细胞机制的支持，该机制在特定应激条件下运行时，会暂时储存错误折叠的多肽，直到它们可以进一步加工：要么重新折叠，要么被蛋白酶水解。更好地理解细胞生理学中的蛋白质聚集，不仅可以更有效地将包涵体形成降至最低以获得更高的可溶性产量，还可以详细了解致力于处理错误折叠危险的细胞机制的复杂性。
