文献类型：期刊文献

英文题名：The rational modification of the secretion pathway: The bidirectional grinding strategy on signal peptide and SecA in Bacillus subtilis

作者：Jiang, Zidong[1];Zhang, Lujia[2];Zhou, Wei[1];Li, Hui[1];Li, Yuanyi[1];Qin, Weichuang[1];Wang, Fengqing[1];Wei, Dongzhi[1];Gao, Bei[1,3]

机构：[1]East China Univ Sci & Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China;[3]East China Univ Sci & Technol, POB 311,130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：191

外文期刊名：BIOCHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20230113334665);WOS:【SCI-EXPANDED(收录号:WOS:000920455600001)】；

基金：Acknowledgements This work was supported by the National Key R&D Program of China (grant no. 2020YFA0908400) , National Natural Foundation of China (No. 31772007) and the Natural Science Foundation of Shanghai (No. 21ZR1416500) .

语种：英文

外文关键词：Bacillus subtilis; Embedded-Model; Signal peptide; Secretory component; SecA

摘要：The secretory (Sec) pathway is essential for protein translocation in Bacillus subtilis. In contrast to signal peptides (SPs), the key components of the Sec pathway lack excessive attention. Herein, based on the structural and mechanistic insights of SecA with SPs, the "Embedded-Model" was proposed, and the matching behavior was "grinded" to boost heterologous protein secretion efficiency. The binding structure of SecA with a SP was established and analyzed using comprehensive computational biology methods. An interaction-based grinding approach was explored for SP and SecA rational modification. The corresponding AprE exhibited 117.2% and 22.0% higher activities than those obtained using wild-type SP and SecA, respectively. Furthermore, a bidirec-tional grinding strategy was developed for both SPs and SecA. The AprE activity was therefore remarkably increased up to 349.6%. This study provides a novel and promising strategy for optimizing the secretion system and enhancing the secretory production of valuable proteins in B. subtilis.