Cloning and Nucleotide Sequences of Two Genes Involved in the 4″-<i>O</i>-Acylation of Macrolide Antibiotics from<i>Streptomyces thermotolerans</i>

Arisawa, Akira; Kawamura, Naoto; Tsunekawa, Hiroshi; Okamura, Koji; Tone, Hiroshi; Okamoto, Rokuro

doi:10.1271/bbb.57.2020

Cited by 27 publications

(13 citation statements)

References 12 publications

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“…The transcriptional activator SrmR encoded within the spiramycin biosynthetic gene cluster of Streptomyces ambofaciens has been shown to be required for the transcription of at least one of the PKS genes involved in assembly of the spiramycin macrolactone ring (14). The acyB2-encoded regulator of Streptomyces thermotolerans has been shown to activate the expression of the acyltransferase gene involved in biosynthesis of the macrolide antibiotic carbomycin (2). Five regulatory genes associated with the tylosin biosynthetic gene cluster of Streptomyces fradiae have been found (3).…”

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confidence: 99%

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

et al. 2004

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Six putative regulatory genes are located at the flank of the nystatin biosynthetic gene cluster in Streptomyces noursei ATCC 11455. Gene inactivation and complementation experiments revealed that nysRI, nysRII, nysRIII, and nysRIV are necessary for efficient nystatin production, whereas no significant roles could be demonstrated for the other two regulatory genes. To determine the in vivo targets for the NysR regulators, chromosomal integration vectors with the xylE reporter gene under the control of seven putative promoter regions upstream of the nystatin structural and regulatory genes were constructed. Expression analyses of the resulting vectors in the S. noursei wild-type strain and regulatory mutants revealed that the four regulators differentially affect certain promoters. According to these analyses, genes responsible for initiation of nystatin biosynthesis and antibiotic transport were the major targets for regulation. Data from cross-complementation experiments showed that nysR genes could in some cases substitute for each other, suggesting a functional hierarchy of the regulators and implying a cascade-like mechanism of regulation of nystatin biosynthesis.

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confidence: 99%

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

et al. 2004

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“…And the reduced glucose consumption rate easily led to the increase of pH level [24,25]. So the possible reason for the phenomena described above may be that after single supplementation with leucine, large amount of ammonium ion produced by deamination of leucine brought about a notable increase in amino nitrogen, resulting in the After the supplementation of leucine, the isovaleryl acid concentration increased significantly, and the relative content of isovalerylspiramycin also increased markedly, indicating the close relationship between the availability of isovaleric acid and isovalerylspiramycins.…”

Section: Resultsmentioning

confidence: 99%

Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin

Wang

Chu

et al. 2008

Bioprocess Biosyst Eng

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Bitespiramycin, a group of 4''-O-acylated spiramycins with 4''-O-isovalerylspiramycins as the major components, is produced by recombinant spiramycin-producing strain Streptomyces spiramyceticus harboring a 4''-O-acyltransferase gene from a carbomycin-producing strain S. mycarofaciens 1748. The effects of leucine feeding on the bitespiramycin fermentation, especially the synthesis of isovalerylspiramycin components, were investigated. The experiment was initially performed in flask culture under the condition of feeding 15.4 mmol/l of leucine at 72 h fermentation, and the culture without leucine feeding was used as control. When 15.4 mmol/l leucine was fed at 72 h, 51.3 +/- 0.33% total isovalerylspiramycins was recorded compared to 40.9 +/- 0.26% under the control condition after 96 h of fermentation. The improvement of total isovalerylspiramycin content was further achieved in 15 l fermentation when 15.4 mmol/l of leucine was supplemented from 65 to 72 h. These results indicated that isovaleryl group derived from leucine catabolism could act as the precursor of the 4'' side chain of bitespiramycin, which profoundly enhanced the synthesis of isovalerylspiramycins in the bitespiramycin complex.

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“…Two of them (tylS and tylT) were deduced to encode SARPs whereas the other, tylR, was clearly related to acyB2 from S. thermotolerans, producer of carbomycin. The latter gene had already been described as a positive regulator [2], the first to be associated with macrolide antibiotic production. The novelty of finding two SARPs apparently associated with a single biosynthetic pathway was diminished somewhat when tylosin production survived insertional inactivation of tylT, leaving the role(s) of its product yet to be determined [4].…”

Section: Higher Levels Of Controlmentioning

confidence: 99%

Antibiotic production by actinomycetes: the Janus faces of regulation

Cundliffe

2006

J IND MICROBIOL BIOTECHNOL

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This manuscript reviews some of the common regulatory mechanisms that control antibiotic production in actinomycetes. These ubiquitous bacteria, collectively responsible for the earthy smell of soil, are prolific producers of antibiotics and other secondary metabolites. The content of this review is biased towards the author's current research interests, concerning the action of regulatory gene products that control transcription of antibiotic-biosynthetic genes and the associated involvement of low molecular weight signalling molecules of the gamma-butyrolactone family. As a result, much fertile ground remains unturned particularly in the area of environmental monitoring and responses of actinomycetes to stimuli so perceived. Reviews casting a broader net are cited in the text.

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Cloning and Nucleotide Sequences of Two Genes Involved in the 4″-O-Acylation of Macrolide Antibiotics fromStreptomyces thermotolerans

Cited by 27 publications

References 12 publications

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

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

Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin

Antibiotic production by actinomycetes: the Janus faces of regulation

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