title: AvaR2, a pseudo γ-butyrolactone receptor homologue from Streptomyces avermitilis, is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth.
abstract: Avermectins produced by Streptomyces avermitilis are effective anthelmintic agents. The autoregulatory signalling molecule that triggers avermectin biosynthesis is a novel butenolide-type molecule, avenolide, rather than common γ-butyrolactones (GBLs). We identified AvaR2, a pseudo GBL receptor homologue, as an important repressor of avermectin and avenolide biosynthesis and cell growth. AvaR2 directly repressed transcription of aveR (the ave cluster-situated activator gene), aco (a key gene for avenolide biosynthesis), its own gene (avaR2) and two other GBL receptor homologous genes (avaR1 and avaR3) by binding to their promoter regions. The aveR promoter had the highest affinity for AvaR2. A consensus 18 bp ARE (autoregulatory element)-like sequence was found in the AvaR2-binding regions of these five target genes. Eleven novel AvaR2 targets were identified, including genes involved in primary metabolism, ribosomal protein synthesis, and stress responses. AvaR2 bound and responded to endogenous avenolide and exogenous antibiotics jadomycin B (JadB) and aminoglycosides to modulate its DNA-binding activity. Our findings help to clarify the roles of pseudo GBL receptors as pleiotropic regulators and as receptors for new type autoregulator and exogenous antibiotic signal. A pseudo GBL receptor-mediated antibiotic signalling transduction system may be a common strategy that facilitates Streptomyces interspecies communication and survival in complex environments.
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Jianya
authors: J
authors: Zhu
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Di
authors: D
authors: Sun
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Wenshuai
authors: W
authors: Liu
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Zhi
authors: Z
authors: Chen
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Jilun
authors: J
authors: Li
authors: State Key Laboratory of Agrobiotechnology and MOA Key Laboratory of Soil Microbiology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
authors: Ying
authors: Y
authors: Wen
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000871:Anthelmintics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D013302:Streptomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C037481:4-butyrolactone receptor; D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011963:Receptors, GABA-A; D012097:Repressor Proteins; D014157:Transcription Factors; D007559:Ivermectin; C019264:avermectin; D015107:4-Butyrolactone