Enzymatic total synthesis of defucogilvocarcin M and its implications for gilvocarcin biosynthesis.

@article{Pahari2012EnzymaticTS,
  title={Enzymatic total synthesis of defucogilvocarcin M and its implications for gilvocarcin biosynthesis.},
  author={Pallab Pahari and Madan K. Kharel and Micah D. Shepherd and Steven G. Van Lanen and J{\"u}rgen Rohr},
  journal={Angewandte Chemie},
  year={2012},
  volume={51 5},
  pages={
          1216-20
        }
}
Gilvocarcin V (GV, 4) is the major metabolite of Streptomyces griseoflavus Go 3592 and various other Streptomyces species. GV is usually produced along with its minor congeners, gilvocarcin M (3) and gilvocarcin E (5), that vary with respect to their side chain at the C8-position.[1] Several analogues of GV (for example, 6–8, Scheme 1), which are collectively called the gilvocarcin group of natural products, have been isolated from different Streptomyces species. All of these analogues contain… Expand
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TLDR
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TLDR
Various experiments are reported, which include incorporation studies with 18O-labeled precursors and the isolation and structure determination of novel intermediates of gilvocarcin biosynthesis accumulated by mutants, in which two genes encoding monooxygenases responsible for the C-C-bond cleavage of the gil Vocarcin pathway were deleted through targeted PCR. Expand
The complete gene cluster of the antitumor agent gilvocarcin V and its implication for the biosynthesis of the gilvocarcins.
TLDR
This is the first reported gene cluster encoding the biosynthesis of a benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside antibiotic, which lays the foundation for the detailed studies of its intriguing biosynthetic steps and possibly for the generation of gilvocarcin analogues with improved biological activities through combinatorial biosynthesis. Expand
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It is suggested that jadomycin and gilvocarcin biosynthesis diverge later in the respective pathways than previously assumed, and that the 5,6-bond cleavage necessitates the formation of multi-oxygenase complexes consisting of at least 3 and 4 enzymes, respectively. Expand
Total synthesis of the gilvocarcins
Convergent total syntheses of the aryl C-glycoside antibiotics gilvocarcin M (1a) and gilvocarcin V (1b) have been accomplished. Key steps include (1) contrasteric coupling of D-fucofuranosyl acetateExpand
Engineered Biosynthesis of Gilvocarcin Analogues with Altered Deoxyhexopyranose Moieties
TLDR
These findings demonstrate GilGT to be a moderately flexible C-glycosyltransferase able to transfer both d- and l-hexopyranose moieties to the unique angucyclinone-derived benzo[d]naphtho[1,2b]pyran-6-one backbone of the gilvocarcins. Expand
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TLDR
Cytotoxicity profiling of polycarcin V in a panel of 37 tumor cell lines indicated significant antitumoral activity with a pronounced selectivity for non-small-cell lung cancer, breast cancer and melanoma cells. Expand
The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis*
TLDR
These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics. Expand
Gilvocarcins, new antitumor antibiotics. 2. Structural elucidation.
TLDR
The structure of gilvocarcins has been determined by chemical degradation, nmr and mass spectra, and they have a benzonaphtopyran-one system, to which the furanose moiety is linked through a C-C glycosyl bond. Expand
Inactivation of the Ketoreductase gilU Gene of the Gilvocarcin Biosynthetic Gene Cluster Yields New Analogues with Partly Improved Biological Activity
TLDR
The structures of the new gilvocarcin‐type aryl‐C‐glycoside antitumor compounds indicate substrate flexibility of the post‐polyketide synthase modifying enzymes, particularly the C‐ Glycosyltransferase and the enzyme responsible for the sugar ring contraction. Expand
Gilvocarcins, new antitumor antibiotics. 5. Biosynthesis of gilvocarcins: incorporation of 13C-labeled compounds into gilvocarcin aglycones.
TLDR
The biosynthesis of the aglycones of gilvocarcins V and M has been studied with 13C-labeled precursors and a route for their biosynthesis is proposed which involves secondary addition of an alkyl group. Expand
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