Identification of a Gene Negatively Affecting Antibiotic Production and Morphological Differentiation in<i>Streptomyces coelicolor</i>A3(2)

Li, Wencheng; Xin, Ying; Guo, Yuzheng; Yu, Zhen; Zhou, Xing; Deng, Zixin; Kieser, Helen M.; Chater, Keith F.; Tao, Meifeng

doi:10.1128/jb.00933-06

Cited by 43 publications

(34 citation statements)

References 44 publications

(49 reference statements)

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“…As the disruption of chromosomal nsdA resulted in higher productions of Act, CDA, Mmy and spores in S. coelicolor, actII-orf4 mRNA was increased in an nsdA mutant, suggesting that the negative effect of nsdA on Act biosynthesis was exerted at the level of transcription of the pathway-specific activator gene. 25,42 Although the genomic library of S. bingchengensis is under way, the new transcription factors, including pathway-specific regulators of milbemycin A 4 and nanchangmycin biosynthesis cluster, will be identified, which may be correlated with nsdA, suppressing antibiotic production. The elucidation of correlations between nsdA and its corresponding factors could be helpful in enhancing antibiotic yield.…”

Section: Discussionmentioning

confidence: 99%

“…25 Total DNA was isolated from S. bingchengensis_226541, 36 and a DNA fragment containing a coding region for the nsdA was amplified with nsdA R (5¢-CCTCGGCGAAGATGTCCTCC-3¢) and nsdA L (5¢-TCTCCGTCGAGGACCTGGGC-3¢) primers. The amplified fragment was ligated into a pMD18-T vector to obtain the recombinant plasmid, pBC106.…”

Section: Dna Sequencing and Analysismentioning

confidence: 99%

“…25 Subsequent studies showed that nsdA is widely existent and conserved in Streptomyces, such as S. hygroscopicus 10B22, S. spiecies FR-008, S. lividans ZX64, S. aureofaciens 211, S. albus JA3453, S. hygroscopicus 5008, S. avermitilis NRRL8165 and S. coelicolor M145. 26 The disruption of chromosomal nsdA resulted in the overproduction of spores and three of four known S. coelicolor antibiotics of different chemical types.…”

Section: Introductionmentioning

confidence: 99%

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Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

Wang

Guo

et al. 2009

J Antibiot

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To investigate the function of nsdA in Streptomyces bingchengensis, it was cloned and sequenced, which presented an 89.89% identity with that of S. coelicolor. The kRED-mediated PCR-targeting technique was used to create nsdA replacement in the S. bingchengensis_226541 chromosome. The nsdA disruption mutant, BC29, was obtained, which produced more pigment and spores than did the ancestral strain. HPLC analysis revealed that the disruption of nsdA efficiently increased milbemycin A 4 production and nanchangmycin production by 1.5-fold and 9-fold, respectively. Complementation of the nsdA mutation restored the phenotype and antibiotic production. These results showed that nsdA negatively affected sporulation and antibiotic production in S. bingchengensis.

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Section: Discussionmentioning

confidence: 99%

Section: Dna Sequencing and Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

Wang

Guo

et al. 2009

J Antibiot

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“…AbsA2 and PhoP repress the transcription of cdaR (Sheeler et al, 2005;Allenby et al, 2012), while AfsQ1 activates its transcription via binding upstream of cdaR (Wang et al, 2013). Other regulators, such as AbrA2, AbrC3 and NsdA, have been proved to affect CDA production indirectly (Yepes et al, 2011;Li et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2)

Gao

et al. 2016

Microbiology

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SCO6256 belongs to the GntR family and shows 74 % identity with SCO6974, which is the repressor of myo-inositol catabolism in Streptomyces coelicolor A3(2). Disruption of SCO6256 significantly enhanced the transcription of myo-inositol catabolic genes in R2YE medium. The purified recombinant SCO6256 directly bound to the upstream regions of SCO2727, SCO6978 and SCO6985, as well as its encoding gene. Footprinting assays demonstrated that SCO6256 bound to the same sites in the myo-inositol catabolic gene cluster as SCO6974. The expression of SCO6256 was repressed by SCO6974 in minimal medium with myo-inositol as the carbon source, but not in R2YE medium. Glutathione-S-transferase pull-down assays demonstrated that SCO6974 and SCO6256 interacted with each other; and both of the proteins controlled the transcription of myo-inositol catabolic genes in R2YE medium. These results indicated SCO6256 regulates the transcription of myo-inositol catabolic genes in coordination with SCO6974 in R2YE medium. In addition, SCO6256 negatively regulated the production of actinorhodin and calcium-dependent antibiotic via control of the transcription of actII-ORF4 and cdaR. SCO6256 bound to the upstream region of cdaR and the binding sequence was proved to be TTTCGGCACGCAGACAT, which was further confirmed through base substitution. Four putative targets (SCO2652, SCO4034, SCO4237 and SCO6377) of SCO6256 were found by screening the genome sequence of Strep. coelicolor A3(2) based on the conserved binding motif, and confirmed by transcriptional analysis and electrophoretic mobility shift assays. These results revealed that SCO6256 is involved in the regulation of myo-inositol catabolic gene transcription and antibiotic production in Strep. coelicolor A3(2).

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“…The genetically well-studied strain Streptomyces coelicolor A3(2) produces at least four chemically distinct classes of antibiotics: the bluepigmented polyketide actinorhodin, the red-pigmented undecylprodigiosins, the lipopeptide calcium-dependent antibiotic (CDA) and the cyclopentanone antibiotic methylenomycin. The triggering of antibiotic biosynthesis in Streptomyces species is generally tightly linked with the initiation of morphological differentiation, and both processes are subject to genetic modulation via a hierarchical regulatory network, integrating various physiological and environmental signals (Li et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor

Yang

Wang

et al. 2010

Microbiology

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HpdR, an IclR-family regulator in Streptomyces coelicolor, is a substrate-dependent repressor for the tyrosine catabolic gene hppD. In this study, S1 nuclease protection assays revealed that hpdR is subject to a negative autoregulation. Purified HpdR showed specific DNA-binding activity for the promoter region of hpdR, indicating that the autoregulation of hpdR is performed directly. The disruption of hpdR led to reduced production of CDA by S. coelicolor J1501, suggesting a positive effect of hpdR on CDA biosynthesis. Electrophoretic mobility shift assays showed that HpdR specifically bound to the promoter region of hmaS (SCO3229 in the CDA gene cluster), encoding 4-hydroxymandelic acid synthase. Disruption of hmaS in J1501 abolished CDA production. It is possible that hpdR regulates CDA biosynthesis by controlling the transcription of hmaS.

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Identification of a Gene Negatively Affecting Antibiotic Production and Morphological Differentiation inStreptomyces coelicolorA3(2)

Abstract: SC7A1 is a cosmid with an insert of chromosomal DNA from Streptomyces coelicolor A3(2). Its insertion into

Cited by 43 publications

References 44 publications

Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2)

Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor

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