A novel valanimycin-resistance determinant (vlmF) from Streptomyces viridifaciens MG456-hF10 The GenBank accession number for the sequence in this paper is AF148322.

Ma, Yunqing; Patel, Jaynish; Parry, Ronald J.

doi:10.1099/00221287-146-2-345

Cited by 18 publications

(20 citation statements)

References 29 publications

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“…and the isobutyl CH 3 resonance for C-6 at 1.04 p.p.m. These values are consistent with the proton chemical shifts exhibited by authentic valanimycin (Garg et al, 2009;Ma & Parry, 2000). Finally the compound was shown to be valanimycin by LC-MS analysis of the crude ethyl acetate extract on a Bruker MicroTOF mass spectrometer, as described previously (Garg et al, 2009).…”

supporting

confidence: 82%

“…The functions of the products of eight of these genes have now been established. VlmF, which is a member of the major facilitator family of transport proteins, confers valanimycin resistance (Ma & Parry, 2000). VlmD, VlmH and VlmR catalyse the conversion of valine into isobutylhydroxylamine (Garg et al, 2002), while VlmL catalyses the formation of L-seryl-tRNA from L-serine (Garg et al, 2006).…”

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confidence: 99%

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Regulation of valanimycin biosynthesis in Streptomyces viridifaciens: characterization of VlmI as a Streptomyces antibiotic regulatory protein (SARP)

Garg

Parry

2010

Microbiology

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Streptomyces antibiotic regulatory proteins (SARPs) have been shown to activate transcription by binding to a tandemly arrayed set of heptameric direct repeats located around the −35 region of their cognate promoters. Experimental evidence is presented here showing that vlmI is a regulatory gene in the valanimycin biosynthetic gene cluster of Streptomyces viridifaciens and encodes a protein belonging to the SARP family. The organization of the valanimycin biosynthetic gene cluster suggests that the valanimycin biosynthetic genes are located on three potential transcripts, vlmHORBCD, vlmJKL and vlmA. Disruption of vlmI abolished valanimycin biosynthesis. Western blot analyses showed that VlmR and VlmA are absent from the vlmI mutant and that the production of VlmK is severely diminished. These results demonstrate that the expression of these genes from the three potential transcripts is under the positive control of VlmI. The vlmA–vlmH and vlmI–vlmJ intergenic regions both exhibit a pattern of heptameric direct repeats. Gel shift assays with VlmI overproduced in Escherichia coli as a C-terminal FLAG-tagged protein clearly demonstrated that VlmI binds to DNA fragments from both regions that contain these heptameric repeats. When a high-copy-number vlmI expression plasmid was introduced into Streptomyces coelicolor M512, which contains mutations in the undecylprodigiosin and actinorhodin activators redD and actII-orf4, undecylprodigiosin production was restored, showing that vlmI can complement a redD mutation. Introduction of the same vlmI expression plasmid into an S. viridifaciens vlmI mutant restored valanimycin production to wild-type levels.

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confidence: 82%

Section: Introductionmentioning

confidence: 99%

Regulation of valanimycin biosynthesis in Streptomyces viridifaciens: characterization of VlmI as a Streptomyces antibiotic regulatory protein (SARP)

Garg

Parry

2010

Microbiology

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“…The functions of five proteins encoded by these genes have been elucidated. These functions include a valine decarboxylase (VlmD) (10), a two-component flavin monooxygenase (VlmH, VlmR) that converts isobutylamine to isobutylhydroxylamine (11)(12)(13), and a valanimycin resistance gene (VlmF) (14). A novel and intriguing feature of the valanimycin biosynthetic gene cluster is the presence of a gene (vlmL) that appears to encode a class II seryl-tRNA synthetase (10).…”

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confidence: 99%

Investigations of valanimycin biosynthesis: Elucidation of the role of seryl-tRNA

Garg¹,

Qian²,

Alemany³

et al. 2008

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

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107

114

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The antibiotic valanimycin is a naturally occurring azoxy compound produced by Streptomyces viridifaciens MG456-hF10. Precursor incorporation experiments showed that valanimycin is derived from L-valine and L-serine via the intermediacy of isobutylamine and isobutylhydroxylamine. Enzymatic and genetic investigations led to the cloning and sequencing of the valanimycin biosynthetic gene cluster, which was found to contain 14 genes. A novel feature of the valanimycin biosynthetic gene cluster is the presence of a gene (vlmL) that encodes a class II seryl-tRNA synthetase. Previous studies suggested that the role of this enzyme is to provide seryl-tRNA for the valanimycin biosynthetic pathway. Here, we report the results of investigations to elucidate the role of seryltRNA in valanimycin biosynthesis. A combination of enzymatic and chemical studies has revealed that the VlmA protein encoded by the valanimycin biosynthetic gene cluster catalyzes the transfer of the seryl residue from seryl-tRNA to the hydroxyl group of isobutylhydroxylamine to produce the ester O-seryl-isobutylhydroxylamine. These findings provide an example of the involvement of an aminoacyl-tRNA in an antibiotic biosynthetic pathway.Streptomyces ͉ aminoacyl-tRNA ͉ antibiotics

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“…The functions of five proteins encoded by these genes have been elucidated. These functions include a valine decarboxylase (VlmD) (21), a twocomponent flavin monooxygenase that converts isobutylamine to isobutylhydroxylamine (VlmH, VlmR) (18 -20), a valanimycin resistance gene (VlmF) (22), and a Streptomyces antibiotic regulatory protein (VlmI) that regulates valanimycin production. 3 The identity of the gene(s) responsible for the formation of the novel N-N bond that is present in valanimycin has thus far remained elusive.…”

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Biochemical Characterization of VlmL, a Seryl-tRNA Synthetase Encoded by the Valanimycin Biosynthetic Gene Cluster

Garg

González

Parry

2006

Journal of Biological Chemistry

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Previous studies have shown that the valanimycin producer Streptomyces viridifaciens contains two genes encoding proteins that are similar to seryl-tRNA synthetases (SerRSs). One of these proteins (SvsR) is presumed to function in protein biosynthesis, because it exhibits a high degree of similarity to the single SerRS of Streptomyces coelicolor. The second protein (VlmL), which exhibits a low similarity to the S. coelicolor SerRS, is hypothesized to play a role in valanimycin biosynthesis, because the vlmL gene resides within the valanimycin biosynthetic gene cluster. To investigate the role of VlmL in valanimycin biosynthesis, VlmL and SvsR have been overproduced in soluble form in Escherichia coli, and the biochemical properties of both proteins have been analyzed and compared. Both proteins were found to catalyze a serine-dependent exchange of 32 P-labeled pyrophosphate into ATP and to aminoacylate total E. coli tRNA with L-serine. Kinetic parameters for the two enzymes show that SvsR is catalytically more efficient than VlmL. The results of these experiments suggest that the role of VlmL in valanimycin biosynthesis is to produce seryl-tRNA, which is then utilized for a subsequent step in the biosynthetic pathway. Orthologs of VlmL were identified in two other actinomycetes species that also contain orthologs of the S. coelicolor SerRS. The significance of these findings is herein discussed.

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A novel valanimycin-resistance determinant (vlmF) from Streptomyces viridifaciens MG456-hF10 The GenBank accession number for the sequence in this paper is AF148322.

Cited by 18 publications

References 29 publications

Regulation of valanimycin biosynthesis in Streptomyces viridifaciens: characterization of VlmI as a Streptomyces antibiotic regulatory protein (SARP)

Regulation of valanimycin biosynthesis in Streptomyces viridifaciens: characterization of VlmI as a Streptomyces antibiotic regulatory protein (SARP)

Investigations of valanimycin biosynthesis: Elucidation of the role of seryl-tRNA

Biochemical Characterization of VlmL, a Seryl-tRNA Synthetase Encoded by the Valanimycin Biosynthetic Gene Cluster

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