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

@article{Kharel2011CharacterizationOT,
  title={Characterization of the TDP-D-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-D-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate.},
  author={Madan K. Kharel and Hui Lian and J{\"u}rgen Rohr},
  journal={Organic \& biomolecular chemistry},
  year={2011},
  volume={9 6},
  pages={
          1799-808
        }
}
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… 

Structural characterization of enzymatic products in the dTDP-d-Qui4NFo biosynthetic pathway using electrospray ionization tandem mass spectrometry.

MS provides efficient and simple characterization of important unusual dTDP-sugar biosynthetic pathways in the O-chains of bacterial lipopolysaccharides.

Isolation and elucidation of the chrysomycin biosynthetic gene cluster and altering the glycosylation patterns of tetracenomycins and mithramycin-pathway molecules

The purpose of this research was to investigate the biosynthesis of several type II polyketide compounds with the goal of improving the bioactivities of these drugs through combinatorial biosynthesis.

Target-specific identification and characterization of the putative gene cluster for brasilinolide biosynthesis revealing the mechanistic insights and combinatorial synthetic utility of 2-deoxy-l-fucose biosynthetic enzymes.

This study represents the first demonstration of TDP-2dF biosynthesis at the enzyme and molecular levels, and provides new hope for expanding the structural diversity of brasilinolides by combinatorial biosynthesis.

Elucidation of post-PKS tailoring steps involved in landomycin biosynthesis.

The results revealed that LanM2 acts as a dehydratase and is responsible for concomitant release of the last PKS-tethered intermediate to yield prejadomycin (10), which was confirmed to be a general pathway intermediate of the biosynthesis.

INVESTIGATION OF THE MECHANISM OF ACTION FOR MITHRAMYCIN AND THE BIOSYNTHESIS OF L-REDNOSE IN SAQUAYAMYCINS

The study demonstrated that modification of the 3-side chain modulates DNA binding affinity of MTM analogues, established a minimum MTM binding site on DNA, and revealed MTM DNA recognition is driven by direct (sequence) and not indirect (conformation) readout laying the foundation for subsequent research based on the interaction between MTM,DNA, and the oncogenic transcription factor EWS-FLI1.

Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R

This work has utilized enzyme immobilization techniques and synthesized l-rhodosamine-thymidine diphosphate (TDP) from α-d-glucose-1-TDP using seven enzymes and indicates that the auxiliary P450-type protein SnogN facilitating glycosylation is surprisingly associated with attachment of the neutral sugar l-nogalose rather than the aminosugar l-Nogalamine in nogalamycin biosynthesis.

One-pot four-enzyme synthesis of thymidinediphosphate-l-rhamnose.

A new, robust one-pot four-enzyme synthetic method was developed for thymidinediphosphate-l-rhamnose starting from d-glucose-1-phosphate and studied in detail to provide the first direct evidence for their functions.

Investigating Mithramycin Deoxysugar Biosynthesis: Enzymatic Total Synthesis of TDP‐D‐Olivose

The results revealed that MtmC is a bifunctional enzyme that can perform a 4-ketoreduction necessary for D-olivose biosynthesis besides the previously found C-methyltransfer forD-mycarose biosynthetic.

Angucyclines: Biosynthesis, mode-of-action, new natural products, and synthesis.

The main focus of this article is on new synthetic approaches and biosynthetic investigations, most of which were published between 1997 and 2010, but go beyond, e.g. for some biosyntheses all the way back to the 1980s, to provide the necessary context of information.

Arginine-rhamnosylation as new strategy to activate translation elongation factor P.

It is demonstrated that the modification is needed to develop pathogenicity, making EarP and dTDP-L-rhamnose-biosynthesizing enzymes ideal targets for antibiotic development.

References

SHOWING 1-10 OF 56 REFERENCES

Characterization of TDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase from the D-mycaminose biosynthetic pathway of Streptomyces fradiae: in vitro activity and substrate specificity studies.

The discovery of a previously overlooked gene, tyl1a, encoding an enzyme thought to convert TDP-4-keto-6-deoxy-d-glucose to TDP, a 3, 4-ketoisomerization reaction in the tylosin pathway of Streptomyces fradiae was investigated, and the fact that Tyl1a exhibits a relaxed substrate specificity holds potential for future deoxysugar biosynthetic engineering endeavors.

In vitro characterization of the enzymes involved in TDP-D-forosamine biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa.

The biochemical functions of the five enzymes involved in TDP-D-forosamine formation have now been fully elucidated and reveal that SpnO and SpnN functions as a 2,3-dehydrase and a 3-ketoreductase, respectively.

A Novel NDP-6-deoxyhexosyl-4-ulose Reductase in the Pathway for the Synthesis of Thymidine Diphosphate-d-fucose*

This paper shows that three dTDP-d-fucose synthetic enzymes are encoded by genes in the gene cluster responsible for the synthesis of serotype b-specific polysaccharide in A. actinomycetemcomitans, and identifies the fcd gene encoding a dT DP-4-keto-6-deoxy- d-glucose reductase.

Biosynthesis of dTDP-3-acetamido-3,6-dideoxy-α-D-galactose in Aneurinibacillus thermoaerophilus L420-91T*

The key enzyme in the biosynthesis of dTDP-d-Fucp3NAc has been identified as an isomerase, which converts the 4-keto educt into the 3-ketO product, with concomitant epimerization at C-4 to produce a 6-deoxy-d -xylo configuration.

The X-ray Structure of dTDP-4-Keto-6-deoxy-D-glucose-3,4-ketoisomerase*

The first three-dimensional structure of this sugar isomerase complexed with dTDP and solved to 1.5 Å resolution is described, which assumes an almost jellyfish-like appearance with the sole α-helices representing the tentacles.

Engineered biosynthesis of macrolide derivatives bearing the non-natural deoxysugars 4-epi-D-mycaminose and 3-n-monomethylamino-3-deoxy-D-fucose.

The ability of desosamine pathway enzymes DesV, DesVI, DesVII, and DesVIII to accept substrates with inverted C-4 stereochemistry in the mutant expressing FdtA resulted in formation of macrolide derivatives bearing 4-epi-d-mycaminose, a sugar heretofore unobserved in Nature.

A two-stage one-pot enzymatic synthesis of TDP-L-mycarose from thymidine and glucose-1-phosphate.

A procedure combining six enzymes native to Escherichia coli or Salmonella typhi with five enzymes from Streptomyces fradiae resulted in the biosynthesis of TDP-l-mycarose from glucose-1-phosphate and thymidine, which can be readily applied to the synthesis of other unusual sugars.

Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine.

The results establish TylM1 and DesVI as new members of a small family of enzymes that are capable of catalyzing N,N-dimethylation of an amino group and provide evidence indicating that the methylation catalyzed by AdoMet-dependent methyltransferases proceeds in a stepwise manner and is nucleophilic in nature.

Cloning and Characterization of the Ravidomycin and Chrysomycin Biosynthetic Gene Clusters

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‐members D‐fucofuranose, to the coumarin‐based polyketide derived backbone.
...