title: Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator, AtrA.
abstract: Daptomycin is a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. To reveal the transcriptional regulatory mechanism of daptomycin biosynthesis, we used the biotinylated dptE promoter (dptEp) as a probe to affinity isolate the dptEp-interactive protein AtrA, a TetR family transcriptional regulator, from the proteome of mycelia. AtrA bound directly to dptEp to positively regulate gene cluster expression and daptomycin production. Meanwhile, both ΔatrA and ΔadpA mutants showed bald phenotype and null production of daptomycin. AdpA positively regulated atrA expression by direct interaction with atrA promoter (atrAp), and removal of ArpA in S. roseosporus, a homolog of the A-factor receptor, resulted in accelerated morphological development and increased daptomycin production, suggesting that atrA was the target of AdpA to mediate the A-factor signaling pathway. Furthermore, AtrA was positively autoregulated by binding to its own promoter atrAp. Thus, for the first time at the transcriptional level, we have identified an autoregulator, AtrA, that directly mediates the A-factor signaling pathway to regulate the proper production of daptomycin.
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, Department of Chemical and Biomolecular Engineering, UCLA, Los, Angeles, California 90095, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and xmmao@zju.edu.cn.
authors: Xu-Ming
authors: XM
authors: Mao
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and.
authors: Shuai
authors: S
authors: Luo
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and.
authors: Ri-Cheng
authors: RC
authors: Zhou
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and.
authors: Feng
authors: F
authors: Wang
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and.
authors: Pin
authors: P
authors: Yu
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and.
authors: Ning
authors: N
authors: Sun
authors: the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and the Hangzhou Huadong Medicine Group Biotechnology Institute Company, Ltd., Hangzhou 310011, China.
authors: Xiao-Xia
authors: XX
authors: Chen
authors: Department of Chemical and Biomolecular Engineering, UCLA, Los, Angeles, California 90095.
authors: Yi
authors: Y
authors: Tang
authors: From the College of Life Sciences, Zhejiang University, Hangzhou 310058, China, the Key Laboratory of Microbial Biochemistry and Metabolism Engineering of Zhejiang Province, Hangzhou 310058, China, and lyq@zju.edu.cn.
authors: Yong-Quan
authors: YQ
authors: Li
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D017576:Daptomycin / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D017576:Daptomycin
keywords: Antibiotics; Bacterial Genetics; Gene Regulation; Protein-DNA Interaction; Secondary Metabolism
references: Clin Infect Dis. 2004 Jun 15;38(12):1673-81
references: 15227611
references: Antimicrob Agents Chemother. 2013 Dec;57(12):6378-80
references: 24080651
references: J Bacteriol. 1989 Dec;171(12):6617-24
references: 2592344
references: Gene. 1992 Jul 1;116(1):43-9
references: 1628843
references: J Bacteriol. 1995 Nov;177(21):6083-92
references: 7592371
references: Biosci Biotechnol Biochem. 2005 Mar;69(3):431-9
references: 15784968
references: Microbiology. 2005 May;151(Pt 5):1507-23
references: 15870461
references: Microbiol Mol Biol Rev. 2005 Jun;69(2):326-56
references: 15944459
references: Mol Microbiol. 2005 Oct;58(1):131-50
references: 16164554
references: Microbiology. 2008 Mar;154(Pt 3):905-14
references: 18310036
references: Appl Microbiol Biotechnol. 2008 Aug;80(2):277-86
references: 18560830
references: Mol Microbiol. 2009 May;72(3):710-23
references: 19400773
references: Appl Biochem Biotechnol. 2011 Mar;163(6):729-43
references: 20886375
references: Plasmid. 2011 May;65(3):219-25
references: 21324338
references: J Bacteriol. 2011 Nov;193(22):6358-65
references: 21926228
references: Appl Biochem Biotechnol. 2011 Dec;165(7-8):1725-39
references: 21960274
references: Appl Microbiol Biotechnol. 2012 May;94(3):637-49
references: 22406858
references: J Appl Microbiol. 2012 Jun;112(6):1095-101
references: 22486967
references: DNA Res. 2012 Jun;19(3):259-73
references: 22449632
references: Appl Microbiol Biotechnol. 2012 Oct;96(1):113-21
references: 22246527
references: PLoS One. 2012;7(11):e50562
references: 23226315
references: Microbiol Mol Biol Rev. 2013 Mar;77(1):112-43
references: 23471619
references: J Bacteriol. 2013 May;195(9):2072-8
references: 23457252
references: Appl Environ Microbiol. 2013 Jul;79(13):4159-63
references: 23603676
references: Mol Microbiol. 2004 Jul;53(2):555-72
references: 15228534
references: Biomed Res Int. 2013;2013:479742
references: 24106707
references: Gene. 2014 Jul 10;544(2):208-15
references: 24768321