Open AccessSAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development
Author(s) -
Di Sun,
Jianya Zhu,
Zhi Chen,
Jilun Li,
Ying Wen
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep36915
Subject(s) - streptomyces avermitilis , avermectin , biology , gene , regulator , regulator gene , regulon , streptomyces , genetics , transcriptional regulation , promoter , transcription factor , regulation of gene expression , gene expression , bacteria , anatomy
Avermectins are useful anthelmintic antibiotics produced by Streptomyces avermitilis . We demonstrated that a novel AraC-family transcriptional regulator in this species, SAV742, is a global regulator that negatively controls avermectin biosynthesis and cell growth, but positively controls morphological differentiation. Deletion of its gene, sav_742 , increased avermectin production and dry cell weight, but caused delayed formation of aerial hyphae and spores. SAV742 directly inhibited avermectin production by repressing transcription of ave structural genes, and also directly regulated its own gene ( sav_742 ) and adjacent gene sig8 (sav_741 ). The precise SAV742-binding site on its own promoter region was determined by DNase I footprinting assay coupled with site-directed DNA mutagenesis, and 5-nt inverted repeats ( GCCGA -n 10 /n 12 - TCGGC ) were found to be essential for SAV742 binding. Similar 5-nt inverted repeats separated by 3, 10 or 15 nt were found in the promoter regions of target ave genes and sig8 . The SAV742 regulon was predicted based on bioinformatic analysis. Twenty-six new SAV742 targets were identified and experimentally confirmed, including genes involved in primary metabolism, secondary metabolism and development. Our findings indicate that SAV742 plays crucial roles in not only avermectin biosynthesis but also coordination of complex physiological processes in S. avermitilis .