文献类型：期刊文献

英文题名：Characterization and functional analysis of FruR in Streptomyces lincolnensis: A pleiotropic regulator that links fructose metabolism to lincomycin biosynthesis

作者：Gao, Yu[1];Chen, Lei[1];Zhang, Zhicheng[1];Xu, Nuo[1];Ye, Jiang[1];Wang, Ruida[2];Wu, Haizhen[1];Zhang, Huizhan[1]

机构：[1]East China Univ Sci & Technol, Bioengn Expt Teaching Demonstrat Ctr, Sch Biotechnol, Dept Appl Biol,State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Tarim Univ, Coll Life Sci & Technol, State Key Lab Incubat Base Conservat & Utilizat Bi, Alar 843300, Peoples R China

年份：2026

卷号：417

起止页码：191

外文期刊名：JOURNAL OF BIOTECHNOLOGY

收录：;EI(收录号：20262420885747);WOS:【SCI-EXPANDED(收录号:WOS:001796790500001)】；

基金：This work was supported by the President's Fund of Tarim University (TDZKBS202536, TDZKCX202502), the National Natural Science Foundation of China (NSFC) (32541085, 42406126), the Xinjiang Leading Talent Introduction Program (Key University Talent Recruitment Project) (XJRC-2025-BTJY-YJ-GX-QNQZ-006), and the National Key Research and Development Program of China (2021YFC2100600) .

语种：英文

外文关键词：FruR; Fructose metabolism; Lincomycin biosynthesis; Streptomyces lincolnensis; Transcriptional regulator

摘要：Lincomycin, a clinically important lincosamide antibiotic, is primarily produced by Streptomyces lincolnensis. This study demonstrated that fructose supplementation inhibits lincomycin biosynthesis. Gene function analysis and gene knockout experiments revealed that the fructose metabolism regulator FruR negatively regulates lincomycin biosynthesis. Quantitative real-time PCR, electrophoretic mobility shift assays, DNase I footprinting assays, and indigoidine synthase reporter assays demonstrated that FruR specifically binds to sequence -GYCCGAACSTGT-, repressing transcription of the fructose metabolism operon. Additionally, FruR directly suppresses the expression of lincomycin biosynthetic gene lmbA, thereby inhibiting lincomycin production. FruR also modulates the expression of several genes involved in carbon metabolism, including aceE2, glmU, and murQ, thereby influencing carbon flux and cellular growth. Further experiments revealed that FruR also controls genes related to fatty acid synthesis (icmB) and oxidative stress response (sigR), suggesting its broad physiological role. Collectively, these findings position FruR as a pleiotropic regulator linking primary and secondary metabolism, providing new insights into carbon source-dependent regulation of secondary metabolism and identifying potential targets for metabolic engineering to enhance lincomycin production.