GilR, an Unusual Lactone‐Forming Enzyme Involved in Gilvocarcin Biosynthesis

@article{Kharel2009GilRAU,
  title={GilR, an Unusual Lactone‐Forming Enzyme Involved in Gilvocarcin Biosynthesis},
  author={M. Kharel and Pallab Pahari and H. Lian and J. Rohr},
  journal={ChemBioChem},
  year={2009},
  volume={10}
}
Last at last: The terminal step of the gilvocarcin V (GV) biosynthetic pathway is an unusual lactone formation. Here we show that the enzyme, GilR, dehydrogenates the hemiacetal moiety of pregilvocarcin V to the lactone found in GV by using covalently bound FAD. 
Delineating the earliest steps of gilvocarcin biosynthesis: role of GilP and GilQ in starter unit specificity.
TLDR
In vivo and in vitro investigations of GilP and GilQ show that GilQ confers unique starter unit specificity when catalyzing an early as well as rate limiting step of gilvocarcin biosynthesis. Expand
Baeyer-Villiger C-C bond cleavage reaction in gilvocarcin and jadomycin biosynthesis.
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TLDR
Two enzymes of the gilvocarcin biosynthetic pathway, GilMT and GilM, with unclear functions were investigated by in vitro studies using purified, recombinant enzymes along with synthetically prepared intermediates to identify a pivotal enzyme in the pathway that exhibits dual functionality. Expand
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INVESTIGATING KEY POST-PKS ENZYMES FROM GILVOCARCIN BIOSYNTHETIC PATHWAY
OF DISSERTATION INVESTIGATING KEY POST-PKS ENZYMES FROM GILVOCARCIN BIOSYNTHETIC PATHWAY Gilvocarcin V (GV) belongs to the angucycline class of antibiotics that possesses remarkable anticancer andExpand
Enzymatic total synthesis of defucogilvocarcin M and its implications for gilvocarcin biosynthesis.
TLDR
A complete, one-pot, enzymatic total synthesis of defucogilvocarcin M(1), a model compound that contains the unique chromophore common to all members of the gil Vocarcin group of natural products is reported. 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
Complexity generation during natural product biosynthesis using redox enzymes.
TLDR
This review includes several recently characterized redox enzymes in the biosynthesis of polyketides and nonribosomal peptides that have shown the potential to transform nascent scaffolds into structurally complex final products. Expand
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
Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis† †Electronic supplementary information (ESI) available: The experimental procedures, materials, and characterization of compounds. See DOI: 10.1039/c6sc00771f
Biochemical and structural investigations into the flavoenzyme CrmK reveal a substrate recycling/salvaging mechanism in caerulomycin biosynthesis.
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TLDR
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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
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TLDR
Cross‐feeding experiments in which GE, defuco‐GE, and defucogilvocarcin V (defu co‐GV) were fed to an early blocked mutant of the GV biosynthetic pathway, showed that neither GE nor any of the defUco‐ compounds was an intermediate of the pathway. 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
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A biosynthetic scheme is proposed for the ravidomycin aglycone. Incorporation of 13C-labeled precursors was followed by conventional and 2-dimensional NMR techniques.
ANGUCYCLINES : TOTAL SYNTHESES, NEW STRUCTURES, AND BIOSYNTHETIC STUDIES OF AN EMERGING NEW CLASS OF ANTIBIOTICS
General and recent aspects of chemical syntheses on angucyclinones and selected related natural products are summarized here. In the first part of this review on angucyclines, the chemical reactionExpand
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