文献类型：期刊文献

英文题名：Substrate-Cofactor Synergistic Reorientation and Substrate Tunnel Engineering of SspLCD for Efficient l-Pipecolic Acid Biosynthesis

作者：Gao, Weijie[1];Huang, Ziyan[1];Li, Yanjun[1];Sun, Shuya[1];Liu, Qinghai[1];Wang, Hualei[1];Chen, Rong[2];Wei, Dongzhi[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, New World Inst Biotechnol, Shanghai 200237, Peoples R China;[2]Hangzhou Normal Univ, Sch Publ Hlth & Nursing, Hangzhou 311121, Zhejiang, Peoples R China

年份：2025

卷号：27

期号：31

起止页码：8470

外文期刊名：ORGANIC LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001541358000001)】；

基金：This study was supported by the Science and Technology Commission of Shanghai Municipality (24HC2810400) and the National Natural Science Foundation of China (82173919).

语种：英文

摘要：Homology screening and structural selection identified a novel lysine cyclodeaminase (SspLCD) with high substrate tolerance for l-pipecolic acid (l-PA) synthesis, rapamycin's key intermediate. Mutant M4 (I61V/I94V/I233V/A235S), developed via substrate-cofactor reorientation and tunnel engineering, exhibited 87.3-fold higher catalytic efficiency than the wild-type. At 1,000 mM substrate loading, M4 achieved >99.9% conversion in 3 h, yielding 1,033 gL-1day(-1)-the highest reported l-PA space-time yield to date. This study establishes an industrially viable pathway for efficient l-PA bioproduction.