Effects of the pleiotropic regulator DasR on lincomycin production in Streptomyces lincolnensis.

Autor: Pai H; School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China., Liu Y; School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China., Zhang C; School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China.; Frontiers Science Center for Synthetic Biology, Tianjin University, Tianjin, PR China.; Key Laboratory of System Bioengineering (Tianjin University), Ministry of Education, Tianjin, PR China., Su J; Key Laboratory of the Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan, 750021, China. su_jy@nxu.edu.cn.; College of Life Science, Ningxia University, Yinchuan, 750021, Ningxia, China. su_jy@nxu.edu.cn., Lu W; School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR China. wenyulu@tju.edu.cn.; Frontiers Science Center for Synthetic Biology, Tianjin University, Tianjin, PR China. wenyulu@tju.edu.cn.; Key Laboratory of System Bioengineering (Tianjin University), Ministry of Education, Tianjin, PR China. wenyulu@tju.edu.cn.
Jazyk: angličtina
Zdroj: Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2024 Jun 15; Vol. 108 (1), pp. 373. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1007/s00253-024-13201-7
Abstrakt: The lincoamide antibiotic lincomycin, derived from Streptomyces lincolnensis, is widely used for the treatment of infections caused by gram-positive bacteria. As a common global regulatory factor of GntR family, DasR usually exists as a regulatory factor that negatively regulates antibiotic synthesis in Streptomyces. However, the regulatory effect of DasR on lincomycin biosynthesis in S. lincolnensis has not been thoroughly investigated. The present study demonstrates that DasR functions as a positive regulator of lincomycin biosynthesis in S. lincolnensis, and its overexpression strain OdasR exhibits a remarkable 7.97-fold increase in lincomycin production compared to the wild-type strain. The effects of DasR overexpression could be attenuated by the addition of GlcNAc in the medium in S. lincolnensis. Combined with transcriptome sequencing and RT-qPCR results, it was found that most structural genes in GlcNAc metabolism and central carbon metabolism were up-regulated, but the lincomycin biosynthetic gene cluster (lmb) were down-regulated after dasR knock-out. However, DasR binding were detected with the DasR responsive elements (dre) of genes involved in GlcNAc metabolism pathway through electrophoretic mobility shift assay, while they were not observed in the lmb. These findings will provide novel insights for the genetic manipulation of S. lincolnensis to enhance lincomycin production. KEY POINTS: • DasR is a positive regulator that promotes lincomycin synthesis and does not affect spore production • DasR promotes lincomycin production through indirect regulation • DasR correlates with nutrient perception in S. lincolnensis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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