Chemical modification of ravidomycin and evaluation of biological activities of its derivatives.

Rakhit, Suman; Eng, C. P.; Baker, Hana E.; Singh, Kartar

doi:10.7164/antibiotics.36.1490

Cited by 20 publications

(13 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the biological activities of these compounds have never been investigated in direct comparison, their biological activity data revealed that amino sugar containing gilvocarcin analogues show increased antibiotic/anticancer potency when compared to compounds with neutral or branched neutral sugar moities. 28 Thus, investigation of the deoxysugar biosynthetic enzymes responsible for the production of d -ravidosamine, and characterization of the glycosyltransferase that attaches the sugar to the polyaromatic backbone are particularly important. An in-depth characterization of these enzymes may provide an opportunity to generate new ravidomycin analogues with altered aminosugar residues for structure–activity relationship (SAR) studies.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the TDP-d-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-d-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate

2011

View full text Add to dashboard Cite

Ravidomycin V and related compounds, e.g., FE35A-B, exhibit potent anticancer activities against various cancer cell lines in the presence of visible light. The amino sugar moieties (d-ravidosamine and its analogues, respectively) in these molecules contribute to the higher potencies of ravidomycin and analogues when compared to closely related compounds with neutral or branched sugars. Within the ravidomycin V biosynthetic gene cluster, five putative genes encoding NDP-d-ravidosamine biosynthetic enzymes were identified. Through the activities of the isolated enzymes in vitro, it is demonstrated that ravD, ravE, ravIM, ravAMT and ravNMT encode TDP-d-glucose synthase, TDP-4-keto-6-deoxy-d-glucose-4,6-dehydratase, TDP-4-keto-6-deoxy-d-glucose-3,4-ketoisomerase, TDP-3-keto-6-deoxy-d-galactose-3-aminotransferase, and TDP-3-amino-3,6-dideoxy-d-galactose-N,N-dimethyl-transferase, respectively. A protocol for a one-pot enzymatic synthesis of TDP-d-ravidosamine has been developed. The results presented here now set the stage to produce TDP-d-ravidosamine routinely for glycosylation studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of the TDP-d-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-d-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate

2011

View full text Add to dashboard Cite

show abstract

“…[17] This is a clear indication that the principally more hydrophilic amino sugar moiety plays a crucial role in the enhanced biological activities of RMV compared to its relatives. Such amino compounds also provide better formulation and delivery options, either as salt forms or for the loading into nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Cloning and Characterization of the Ravidomycin and Chrysomycin Biosynthetic Gene Clusters

et al. 2010

View full text Add to dashboard Cite

The gene clusters responsible for the biosynthesis of two anti-tumor antibiotics, ravidomycin and chrysomycin, have been cloned from Streptomyces ravidus and Streptomyces albaduncus, respectively. Sequencing of the 33.28 kb DNA region of the cosmid cosRav32 and the 34.65 kb DNA region of cosChry1-1 and cosChryF2 revealed 36 and 35 open reading frames (ORFs), respectively, harboring tandem sets of type II polyketide synthase (PKS) genes, D-ravidosamine and D-virenose biosynthetic genes, post-PKS tailoring genes, regulatory genes, and genes of unknown function. The isolated ravidomycin gene cluster was confirmed to be involved in ravidomycin biosynthesis through the production of a new analogue of ravidomycin along with anticipated pathway intermediates and biosynthetic shunt products upon heterologous expression of the cosmid, cosRav32, in Streptomyces lividans TK24. The identity of the cluster was further verified through cross complementation of gilvocarcin V (GV) mutants. Similarly, the chrysomycin gene cluster was demonstrated to be indirectly involved in chrysomycin biosynthesis through cross-complementation of gilvocarcin mutants deficient in the oxygenases GilOII, GilOIII, and GilOIV with the respective chrysomycin monooxygenase homologues. The ravidomycin glycosyltransferase (RavGT) appears to be able to transfer both amino-and neutral sugars, exemplified through the structurally distinct 6-membered D-ravidosamine and 5-membered D-fucofuranose, to the coumarin-based polyketide derived backbone. These results expand the library of biosynthetic genes involved in the biosyntheses of gilvocarcin class compounds that can be used to generate novel analogues through combinatorial biosynthesis.

show abstract

“…In the course of our screening program for new antibiotics, a streptomycete, strain S50905, designated as Streptomyces ravidus S50905 was found to produce a new antibiotic, deacetylravidomycin iV-oxide (1), along with ravidomycin (4)x~4) and deacetylravidomycin…”

mentioning

confidence: 99%

Deacetylravidomycin N-oxide, a new antibiotic. Taxonomy and fermentation of the producing organism and isolation, structure and biological properties of the antibiotic.

et al. 1989

View full text Add to dashboard Cite

Streptomyces ravidus S50905was found to produce a new antibiotic, deacetylravidomycin TV-oxide, together with ravidomycin and deacetylravidomycin in a culture mediumcontaining sodiumanthraquinone-/3-sulfonate. The structure of this newcompound was determined from NMRand mass spectrometric data, and further confirmed by chemical synthesis from deacetylravidomycin. Deacetylravidomycin iV-oxide was antitumor active against P388 leukemia and Meth A fibrosarcoma in a wide range of doses, and considerably less toxic than deacetylravidomycin. Its antibacterial activity was less potent than deacetylravidomycin. Ravidomycin JV-oxide was also synthesized from ravidomycin and its biological properties were tested.In the course of our screening program for new antibiotics, a streptomycete, strain S50905, designated as Streptomyces ravidus S50905 was found to produce a new antibiotic, deacetylravidomycin iV-oxide (1), along with ravidomycin (4)x~4) and deacetylravidomycin (2)4). The present paper describes the taxonomy and fermentation of the producing strain and the isolation, physico-chemical properties, structure assignment and biological properties of deacetylravidomycin iV-oxide.Taxonomy

show abstract

Chemical modification of ravidomycin and evaluation of biological activities of its derivatives.

Cited by 20 publications

References 5 publications

Characterization of the TDP-d-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-d-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate

Characterization of the TDP-d-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-d-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate

Cloning and Characterization of the Ravidomycin and Chrysomycin Biosynthetic Gene Clusters

Deacetylravidomycin N-oxide, a new antibiotic. Taxonomy and fermentation of the producing organism and isolation, structure and biological properties of the antibiotic.

Contact Info

Product

Resources

About