A repressor-response regulator gene pair controlling jadomycin B production in Streptomyces venezuelae ISP5230

Yang, Keqian; Han, Lei; He, Jianyong; Wang, Liru; Vining, L. C.

doi:10.1016/s0378-1119(01)00723-5

Cited by 48 publications

(47 citation statements)

References 29 publications

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“…14,28,51−53 The cluster-situated regulatory gene products of jadR1 and jadR2 are involved in cross-regulation of Jd and Cm biosynthesis and are located upstream of the polyketide synthase structural genes. 12,54 We have identified that jadX located upstream of the sugar biosynthetic genes likely codes for an unusual natural product binding protein. It also plays a significant role in the levels of Jd produced in the S. venezuelae ISP5230.…”

Section: ■ Discussionmentioning

confidence: 99%

JadX is a Disparate Natural Product Binding Protein

Robertson¹,

Forget²,

Martinez-Farina³

et al. 2016

J. Am. Chem. Soc.

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Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/eng/view/object/?id=1cef32c4-4c83-4b35-af83-2602ff6d1af3 http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/voir/objet/?id=1cef32c4-4c83-4b35-af83-2602ff6d1af3JadX is a Disparate Natural Product Binding Protein ABSTRACT: We report that JadX, a protein of previously undetermined function coded for in the jadomycin biosynthetic gene cluster of Streptomyces venezuelae ISP5230, affects both chloramphenicol and jadomycin production levels in blocked mutants. Characterization of recombinant JadX through protein−ligand interactions by chemical shift perturbation and WaterLOGSY NMR spectroscopy resulted in the observation of binding between JadX and a series of jadomycins and between JadX and chloramphenicol, another natural product produced by S. venezuelae ISP5230. These results suggest JadX to be an unusual class of natural product binding protein involved in binding structurally disparate natural products. The ability for JadX to bind two different natural products in vitro and the ability to affect production of these secondary metabolites in vivo suggest a potential role in regulation or signaling. This is the first example of functional characterization of these JadX-like proteins, and provides insight into a previously unobserved regulatory process.

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Section: ■ Discussionmentioning

confidence: 99%

JadX is a Disparate Natural Product Binding Protein

Robertson¹,

Forget²,

Martinez-Farina³

et al. 2016

J. Am. Chem. Soc.

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“…To date, no similar situation has been described for type II PKS clusters, including those responsible for angucycline biosynthesis. For example, the S. venezuelae jadomycin, the Streptomyces cyanogenus landomycin A, and the Streptomyces antibioticus oviedomycin biosynthesis clusters, where the structural genes both show strong synteny to those in the alp cluster (30), contain, respectively, three (43,46), two (34), and two (24) regulatory genes, none encoding a SARP. A high degree of synteny was, however, found between four of the alp regulatory genes and those present in the regulatory subcluster controlling tylosin biosynthesis ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Involvement of AlpV, a New Member of the Streptomyces Antibiotic Regulatory Protein Family, in Regulation of the Duplicated Type II Polyketide Synthase alp Gene Cluster in Streptomyces ambofaciens

et al. 2005

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A type II polyketide synthase gene cluster located in the terminal inverted repeats of Streptomyces ambofaciens ATCC 23877 was shown to be responsible for the production of an orange pigment and alpomycin, a new antibiotic probably belonging to the angucycline/angucyclinone class. Remarkably, this alp cluster contains five potential regulatory genes, three of which (alpT, alpU, and alpV) encode proteins with high similarity to members of the Streptomyces antibiotic regulatory protein (SARP) family. Deletion of the two copies of alpV (one in each alp cluster located at the two termini) abolished pigment and antibiotic production, suggesting that AlpV acts as a transcriptional activator of the biosynthetic genes. Consistent with this idea, the transcription of alpA, which encodes a ketosynthase essential for orange pigment and antibiotic production, was impaired in the alpV mutant, while the expression of alpT, alpU, and alpZ, another regulatory gene encoding a ␥-butyrolactone receptor, was not significantly affected. Real-time PCR experiments showed that transcription of alpV in the wild-type strain increases dramatically after entering the transition phase. This induction precedes that of alpA, suggesting that AlpV needs to reach a threshold level to activate the expression of the structural genes. When introduced into an S. coelicolor mutant with deletions of actII-ORF4 and redD, the SARP-encoding genes regulating the biosynthesis of actinorhodin and undecylprodigiosin, respectively, alpV was able to restore actinorhodin production only. However, actII-ORF4 did not complement the alpV mutant, suggesting that AlpV and ActII-ORF4 may act in a different way.

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“…Genes encoding putative transcriptional activators were identified within these clusters (Fedorenko et al, 2000;Trefzer et al, 2002;Westrich et al, 1999;Yang et al, 2001). They are distinct from other members of the SARP family in that they contain a winged helix-turn-helix DNA-binding domain in their C-terminal region (Wietzorreck & Bibb, 1997).…”

Section: Discussionmentioning

confidence: 99%

DNA-binding activity of LndI protein and temporal expression of the gene that upregulates landomycin E production in Streptomyces globisporus 1912

et al. 2005

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The gene lndI is involved in the pathway-specific positive regulation of biosynthesis of the antitumour polyketide landomycin E in Streptomyces globisporus 1912. LndI was overexpressed in Escherichia coli as a protein C-terminally fused to the intein-chitin-binding-domain tag and purified in a one-step column procedure. Results of in vivo LndI titration, DNA gel mobility-shift assays and promoter-probing experiments indicate that LndI is an autoregulatory DNA-binding protein that binds to its own gene promoter and to the promoter of the structural gene lndE. Enhanced green fluorescent protein was used as a reporter to study the temporal and spatial pattern of lndI transcription. Expression of lndI started before cells entered mid-exponential phase and peak expression coincided with maximal accumulation of landomycin E and biomass. In solid-phase analysis, lndI expression was evident in substrate mycelia but was absent from aerial hyphae and spores.

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A repressor-response regulator gene pair controlling jadomycin B production in Streptomyces venezuelae ISP5230

Cited by 48 publications

References 29 publications

JadX is a Disparate Natural Product Binding Protein

JadX is a Disparate Natural Product Binding Protein

Involvement of AlpV, a New Member of the Streptomyces Antibiotic Regulatory Protein Family, in Regulation of the Duplicated Type II Polyketide Synthase alp Gene Cluster in Streptomyces ambofaciens

DNA-binding activity of LndI protein and temporal expression of the gene that upregulates landomycin E production in Streptomyces globisporus 1912

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