Digitoxosyltetracenomycin C and glucosyltetracenomycin C, two novel elloramycin analogues obtained by exploring the sugar donor substrate specificity of glycosyltransferase ElmGT.

@article{Fischer2002DigitoxosyltetracenomycinCA,
  title={Digitoxosyltetracenomycin C and glucosyltetracenomycin C, two novel elloramycin analogues obtained by exploring the sugar donor substrate specificity of glycosyltransferase ElmGT.},
  author={C. Fischer and L. Rodr{\'i}guez and E. P. Patallo and Fredilyn M Lipata and A. Bra{\~n}a and C. M{\'e}ndez and J. Salas and J. Rohr},
  journal={Journal of natural products},
  year={2002},
  volume={65 11},
  pages={
          1685-9
        }
}
Our explorations of glycosyltransferase ElmGT from Streptomyces olivaceus Tü 2353, which shows an interesting flexibility regarding its sugar donor substrate, were extended toward various previously unexplored sugar co-substrates. The studies revealed that ElmGT, which normally transfers L-rhamnose to 8-demethyltetracenomycin C as a crucial biosynthetic step in elloramycin biosynthesis, is also able to process an activated non-deoxygenated sugar, NDP-D-glucose, as well as NDP-L-digitoxose… Expand
Ketoolivosyl-tetracenomycin C: a new ketosugar bearing tetracenomycin reveals new insight into the substrate flexibility of glycosyltransferase ElmGT.
TLDR
This report represents the first characterization of a tetracenomycin derivative decorated with a ketosugar moiety, and gives further insight into the substrate flexibility of ElmGT to include an NDP-ketosugar, which is unusual and is rarely observed among glycosyltransferases from antibiotic biosynthetic pathways. Expand
Development of a Streptomyces venezuelae-Based Combinatorial Biosynthetic System for the Production of Glycosylated Derivatives of Doxorubicin and Its Biosynthetic Intermediates †
TLDR
A range of doxorubicin analogs containing diverse deoxysugar moieties, seven of which are novel rhodomycin D derivatives, were generated and demonstrates the potential of the S. venezuelae-based combinatorial biosynthetic system for modifying structurally complex sugar moieties attached to anthracyclines as an alternative to chemical syntheses for improving anticancer agents. Expand
Engineered biosynthesis of glycosylated derivatives of narbomycin and evaluation of their antibacterial activities
TLDR
New insight is provided into the functions of deoxysugar biosynthetic enzymes and structure–activity relationships of the sugar moieties attached to the macrolides and the potential of combinatorial biosynthesis for the generation of new macrolide carrying diverse sugars with increased antibacterial activities is demonstrated. Expand
Modulation of Deoxysugar Transfer by the Elloramycin Glycosyltransferase ElmGT through Site-Directed Mutagenesis
TLDR
Site-directed mutagenesis in residues L309 and N312, located in the alpha/beta/alpha motif within the nucleoside diphosphate-sugar binding region, can be used to modulate the substrate flexibility of ElmGT, making it more precise for transfer of specific deoxysugars. Expand
Isolation and elucidation of the chrysomycin biosynthetic gene cluster and altering the glycosylation patterns of tetracenomycins and mithramycin-pathway molecules
TLDR
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. Expand
Deciphering the late steps in the biosynthesis of the anti‐tumour indolocarbazole staurosporine: sugar donor substrate flexibility of the StaG glycosyltransferase
TLDR
Staurosporine biosynthesis was reconstituted in vivo in a heterologous host Streptomyces albus by using two different plasmids: the ‘aglycone vector’ expressing a set of genes involved in indolocarbazole biosynthesis together with staG (encoding a glycosyltransferase) and/or staN (coding for a P450 oxygenase). Expand
Glycosylated Derivatives of Steffimycin: Insights into the Role of the Sugar Moieties for the Biological Activity
TLDR
Analysis of the biological activities of these compounds against three human tumor cell lines revealed two of them, 3′‐O‐methylsteffimycin and D‐digitoxosyl‐8‐demethoxy‐10‐deoxysteffIMycinone, to possess improved antitumor activities. Expand
Engineering biosynthetic pathways for deoxysugars: branched-chain sugar pathways and derivatives from the antitumor tetracenomycin.
TLDR
Formation of two compounds represents examples of the sugar cosubstrate flexibility of the ElmGT glycosyltransferase, and provided insights into the substrate flexibility of deoxysugar biosynthesis enzymes as the C-methyltransferases EryBIII and MtmC, the epimerases OleL and EryBVII, and the 4-ketoreductases ERYV and OleU. Expand
Deciphering biosynthesis of the RNA polymerase inhibitor streptolydigin and generation of glycosylated derivatives.
TLDR
The biosynthetic gene cluster for the dienoyltetramic acid streptolydigin was identified and characterized from the producer organism Streptomyces lydicus NRRL2433, with a certain degree of flexibility of the L-rhodinosyl transferase SlgG for the recognition of 2,3, 6-trideoxyhexoses and 2,6-dideoxy hexoses, both in D- and L- configuration. Expand
Chapter 12. The power of glycosyltransferases to generate bioactive natural compounds.
TLDR
A strategy to explore new GTs is presented as well as strategies to generate artificial GTs either randomly or in a rational design leading to novel unnatural bioactive compounds. Expand
...
1
2
3
4
5
...