Cloning and characterization of a gene cluster for geldanamycin production in<i>Streptomyces hygroscopicus</i>NRRL 3602

Rascher, Andreas; Hu, Zhihao; Viswanathan, N.; Schirmer, Andreas; Reid, Ralph; Nierman, William C.; Lewis, Matthew R.; Hutchinson, C. Richard

doi:10.1016/s0378-1097(02)01148-5

Cited by 144 publications

(152 citation statements)

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“…53 Two AHBA biosynthesis clusters, one (AHBA-N) associated with putative naphthomycin biosynthesis and the other (AHBA-B) functionally, although not physically, associated with geldanamycin (gdn) biosynthesis genes, were isolated from S. hygroscopicus. [54][55][56] Curiously, the AHBA-B subcluster contains two copies of an aminoDHQ synthase gene (rifG homolog), but lacks an amino-DAHP synthase gene (rifH). 53 A rifH homolog is also missing from the AHBA synthesis genes of the mitomycin cluster.…”

Section: The Ahba Synthesis Gene Clustersmentioning

confidence: 99%

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

2010

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The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.

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Section: The Ahba Synthesis Gene Clustersmentioning

confidence: 99%

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

2010

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“…17 This superfamily represents a large group of proteins containing a similar fold but diverse functions, making putative functional analysis by homology ambiguous. The BLASTP search identified a series of similar proteins coded for in other secondary metabolite biosynthetic pathways including azicemicin, 21 geldanamycin, 22 herbimycin, 23 kinamycin, 24 and methylenomycin ( Figure S1). 25,26 A full sequence alignment of these JadX homologues is presented in the Figure S2.…”

Section: ■ Introductionmentioning

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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“…Biosynthesis of this class of compounds involves the assembly of 3-amino-5-hydroxybenzoic acid as a starter unit. Following elongation with the acyl-Coenzyme A substrates malonyl-CoA, methylmalonyl-CoA, and 2-methoxymalonyl-CoA (ACP) [12ϳ14], the presumed polyketide intermediate undergoes intramolecular lactamization by GdmF to form progeldanamycin [15], an initial polyketide synthase (PKS) product, which is, then converted to GDM by several post-PKS modification steps, such as C-17 hydroxylation, C-17 O-methylation, C-21 oxidation, C-7 carbamoylation, and C-4, 5 oxidation [15ϳ17].…”

Section: Introductionmentioning

confidence: 99%

“…[15,19,20]. Analysis of the GDM biosynthetic gene cluster has revealed the presence of a series of putative post-PKS modifying genes from S. hygroscopicus var.…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of the GDM biosynthetic gene cluster has revealed the presence of a series of putative post-PKS modifying genes from S. hygroscopicus var. geldanus NRRL 3602 [15]. The genetic manipulation of the gene or domain of the GDM biosynthetic gene cluster is helpful for understanding the biosynthesis process, and creates new analogues of GDM [16,18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A New Post-PKS Modification Process in the Carbamoyltransferase Gene Inactivation Strain of Streptomyces hygroscopicus 17997

Wang

et al. 2008

J Antibiot

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Genetic manipulation of geldanamycin (GDM) producer Streptomyces species is a rational approach to understand biosynthesis processes and create new analogues. In this study, the carbamoyltransferase gene gdmN was inactivated by insertion of an apramycinresistance gene aac3 (IV) into the genome of the geldanamycin-producing strain Streptomyces hygroscopicus 17997. GDM analogues produced by this mutant strain were isolated and characterized, such as new compound 4,5-dihydro-7-O -descarbamoyl-7-hydroxy-19-Oglycylgeldanamycin. This compound could be converted to compound 4,5-dihydro-19-O-glycylgeldanamycin, another new GDM analogue, by a strain of Streptomyces hygroscopicus 17997 in which the GDM-pks was inactivated. These new compounds exhibited reductions of cytotoxicity against HepG2 cancer cells, but increases of aqueous solubility. These results suggest that a new postpolyketide synthase modification was involved in this process to produce new GDM analogues.

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Cloning and characterization of a gene cluster for geldanamycin production inStreptomyces hygroscopicusNRRL 3602

Cited by 144 publications

References 42 publications

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

JadX is a Disparate Natural Product Binding Protein

A New Post-PKS Modification Process in the Carbamoyltransferase Gene Inactivation Strain of Streptomyces hygroscopicus 17997

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