Institute of Biochemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Department of Chemistry and Biology, Korea Science Academy of Korea Advanced Institute of Science and Technology, Busan 47162, South Korea.
Biotechnol Adv. 2021 Dec;53:107864. doi: 10.1016/j.biotechadv.2021.107864. Epub 2021 Nov 10.
Bacteria have evolved a diverse range of secretion systems to export different substrates across their cell envelope. Although secretion of proteins into the extracellular space could offer advantages for recombinant protein production, the low secretion titers of the secretion systems for some heterologous proteins remain a clear drawback of their utility at commercial scales. Therefore, a potential use of most of secretion systems as production platforms at large scales are still limited. To overcome this limitation, remarkable efforts have been made toward improving the secretion efficiency of different bacterial secretion systems in recent years. Here, we review the progress with respect to biotechnological applications of type I secretion system (T1SS) of Gram-negative bacteria. We will also focus on the applicability of T1SS for the secretion of heterologous proteins as well as vaccine development. Last but not least, we explore the employed engineering strategies that have enhanced the secretion efficiencies of T1SS. Attention is also paid to directed evolution approaches that may offer a more versatile approach to optimize secretion efficiency of T1SS.
细菌已经进化出多种分泌系统,以将不同的底物输出到其细胞包膜。虽然将蛋白质分泌到细胞外空间可以为重组蛋白生产带来优势,但某些异源蛋白质的分泌系统的低分泌效价仍然是其在商业规模上应用的明显缺点。因此,大多数分泌系统作为大规模生产平台的潜在用途仍然有限。为了克服这一限制,近年来人们做出了巨大努力来提高不同细菌分泌系统的分泌效率。在这里,我们回顾了革兰氏阴性菌 I 型分泌系统(T1SS)在生物技术应用方面的进展。我们还将重点介绍 T1SS 在分泌异源蛋白和疫苗开发方面的适用性。最后但同样重要的是,我们探讨了提高 T1SS 分泌效率所采用的工程策略。我们还关注定向进化方法,该方法可能为优化 T1SS 的分泌效率提供更通用的方法。