In Vivo Analysis of the Regulatory Genes in the Nystatin Biosynthetic Gene Cluster of
            <i>Streptomyces noursei</i>
            ATCC 11455 Reveals Their Differential Control Over Antibiotic Biosynthesis

Sekurova, Olga N.; Brautaset, Trygve; Sletta, Håvard; Borgos, Sven Even F.; Jakobsen, Øyvind Mejdell; Ellingsen, Trond E.; Strøm, Arne R.; Valla, Svein; Zotchev, Sergey B.

doi:10.1128/jb.186.5.1345-1354.2004

Cited by 99 publications

(82 citation statements)

References 40 publications

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“…However, because the mutation left some synthesis of erythromycin intact, it differs from deletions of activators in many streptomycetes that abolish the production of an antibiotic completely (3,23). Our observations more closely resemble the case of S. noursei, in which a strain with a deletion of a nystatin synthesis regulator still produced some antibiotic (24).…”

Section: Recombinant Bldd Binds To Ery Promoters and To Its Own Promosupporting

confidence: 56%

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Chng

Lum

Vroom

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Saccharopolyspora erythraea makes erythromycin, an antibiotic commonly used in human medicine. Unusually, the erythromycin biosynthetic (ery) cluster lacks a pathway-specific regulatory gene. We isolated a transcriptional regulator of the ery biosynthetic genes from S. erythraea and found that this protein appears to directly link morphological changes caused by impending starvation to the synthesis of a molecule that kills other bacteria, i.e., erythromycin. DNA binding assays, liquid and affinity chromatography, MALDI-MS analysis, and de novo sequencing identified this protein (M r ‫؍‬ 18 kDa) as the S. erythraea ortholog of BldD, a key regulator of development in Streptomyces coelicolor. Recombinant S. erythraea BldD bound to all five regions containing promoters in the ery cluster as well as to its own promoter, the latter with an order-of-magnitude stronger than to the ery promoters. Deletion of bldD in S. erythraea decreased the erythromycin titer in a liquid culture 7-fold and blocked differentiation on a solid medium. Moreover, an industrial strain of S. erythraea with a higher titer of erythromycin expressed more BldD than a wild-type strain during erythromycin synthesis. Together, these results suggest that BldD concurrently regulates the synthesis of erythromycin and morphological differentiation. The ery genes are the first direct targets of a BldD ortholog to be identified that are positively regulated.cell differentiation ͉ secondary metabolites ͉ BldD

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Section: Recombinant Bldd Binds To Ery Promoters and To Its Own Promosupporting

confidence: 56%

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Chng

Lum

Vroom

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The latter has been described for PKSI-encoding genes from the nystatin biosynthesis gene cluster of S. norsei. 7 In the case of S. viridochromogenes GW4-C1, no PCR fragment was obtained for aviM, aviGT3 and aviC2, whereas very tiny fragments Production of Avilamycin A Y Rebets et al were obtained for aviD, aviRa and aviC1 (Figure 2c). In the case of S. viridochromogenes GW4-C2, no PCR fragment was obtained for aviM, aviRa, aviGT3 and aviC2, whereas very tiny fragments were obtained for aviD and aviC1 (Figure 2d).…”

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confidence: 97%

“…[4][5][6] Recent efforts in cloning and characterization of biosynthetic gene clusters for new groups of secondary metabolites revealed novel classes of transcriptional factors that differ from typical SARPs or LAL representatives. 7,8 Avilamycins are secondary metabolites produced by Streptomyces viridochromogenes Tu57. They are active against Gram-positive bacteria.…”

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confidence: 99%

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Production of Avilamycin A is regulated by AviC1 and AviC2, two transcriptional activators

et al. 2009

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Streptomycetes are typical soil-dwelling bacteria with intricate morphological and biochemical differentiation of colonies, resulting in onset of secondary metabolite production. Compounds produced during these stages of differentiation comprise nearly two-thirds of bioactive molecules synthesized by microorganisms, including antibiotics, antitumor agents and immunosuppressants. 1,2 The biosynthesis of antibiotics and other secondary metabolites is controlled by interactions of both global and pathway-specific regulators. However, in all cases, the influence of the environment is reflected by the activity of pathway-specific regulatory genes, which are located within a biosynthetic gene cluster and which control the expression of biosynthetic genes. 3 On account of high structural and functional similarity, such regulators were grouped into two families, namely Streptomyces antibiotics regulatory proteins (SARP), mostly found within the aromatic polyketides clusters, and large ATP-binding regulators of LuxR family (LAL), controlling the production of macrolides and glycopeptides. [4][5][6] Recent efforts in cloning and characterization of biosynthetic gene clusters for new groups of secondary metabolites revealed novel classes of transcriptional factors that differ from typical SARPs or LAL representatives. 7,8 Avilamycins are secondary metabolites produced by Streptomyces viridochromogenes Tu57. They are active against Gram-positive bacteria. It is known that avilamycins bind to the 23S rRNA in the region proximal to the channel, where tRNA enters the A-site and blocks the protein synthesis. 9 Avilamycin resistance is mediated by 23S rRNA methylation and active avilamycin transport. 10 The avilamycin resistance genes together with the structural genes were identified and cloned as an entire biosynthetic gene cluster containing 54 open reading frames. 11 The biosynthetic steps leading to the formation of the avilamycin molecule were established by the analysis of secondary metabolites produced by mutants. 11,12 Within the cluster also, two putative regulatory genes named aviC1 and aviC2 were identified. Both genes are located in close proximity to each other and are transcribed in the same direction (Figure 1). Genes are separated by a 271-bp non-coding region. We succeeded in identifying the presence of putative bacterial promoter sequences upstream of aviC1 initiation codon by the use of BPROM bacterial promoter prediction server (Softberry Inc., Mount Kisco, NY, USA). It consists of a putative À10 box GGTTTTCAT (Score 34) and a À35 box ATGCGA (Score 12). Another putative promoter sequence is located upstream of the aviC2 translation start site consisting of a À10 box GCCCATGAT (Score 31) and a À35 box at TTTCTA (Score 34) similar to consensus Streptomycetes promoters. 13

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“…These results indicated that both gdmRI and gdmRII were positive regulatory genes of the geldanamycin biosynthesis. AveR [7] , RapH [8] , MonH [9] , PikD [10] , PimR [11] 以及 NysRI 和 NusRII [12] 等, 它们与链霉菌抗生素调控蛋 …”

mentioning

confidence: 99%

Regulatory Genes of Geldanamycin Biosynthesis

Lei

Liu

et al. 2008

Chinese Journal of Biotechnology

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In Vivo Analysis of the Regulatory Genes in the Nystatin Biosynthetic Gene Cluster of Streptomyces noursei ATCC 11455 Reveals Their Differential Control Over Antibiotic Biosynthesis

Cited by 99 publications

References 40 publications

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Production of Avilamycin A is regulated by AviC1 and AviC2, two transcriptional activators

Regulatory Genes of Geldanamycin Biosynthesis

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