{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T19:03:23Z","timestamp":1788721403640,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["grant no. 31170045"],"award-info":[{"award-number":["grant no. 31170045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Avermectins produced by <jats:italic>Streptomyces avermitilis<\/jats:italic> are effective anthelmintic agents. The autoregulatory signalling molecule that triggers avermectin biosynthesis is a novel butenolide\u2010type molecule, avenolide, rather than common \u03b3\u2010butyrolactones (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 <jats:italic>aveR<\/jats:italic> (the <jats:italic>ave<\/jats:italic> cluster\u2010situated activator gene), <jats:italic>aco<\/jats:italic> (a key gene for avenolide biosynthesis), its own gene (<jats:italic>avaR2<\/jats:italic>) and two other GBL receptor homologous genes (<jats:italic>avaR1<\/jats:italic> and <jats:italic>avaR3<\/jats:italic>) by binding to their promoter regions. The <jats:italic>aveR<\/jats:italic> promoter had the highest affinity for AvaR2. A consensus 18 bp ARE (<jats:styled-content>a<\/jats:styled-content>uto<jats:styled-content>r<\/jats:styled-content>egulatory <jats:styled-content>e<\/jats:styled-content>lement)\u2010like sequence was found in the AvaR2\u2010binding 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\u2010binding 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\u2010mediated antibiotic signalling transduction system may be a common strategy that facilitates <jats:italic>Streptomyces<\/jats:italic> interspecies communication and survival in complex environments.<\/jats:p>","DOI":"10.1111\/mmi.13479","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T08:36:46Z","timestamp":1470731806000},"page":"562-578","source":"Crossref","is-referenced-by-count":47,"title":["AvaR2, a pseudo \u03b3\u2010butyrolactone receptor homologue from <i>Streptomyces avermitilis<\/i>, is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth"],"prefix":"10.1111","volume":"102","author":[{"given":"Jianya","family":"Zhu","sequence":"first","affiliation":[{"name":"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 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Agricultural University Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilun","family":"Li","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wen","sequence":"additional","affiliation":[{"name":"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 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