The aureolic acid family of antitumor compounds: structure, mode of action, biosynthesis, and novel derivatives

@article{Lomb2006TheAA,
  title={The aureolic acid family of antitumor compounds: structure, mode of action, biosynthesis, and novel derivatives},
  author={Felipe Lomb{\'o} and Nuria Men{\'e}ndez and Jos{\'e} A Salas and Carmen M{\'e}ndez},
  journal={Applied Microbiology and Biotechnology},
  year={2006},
  volume={73},
  pages={1-14}
}
Members of the aureolic acid family are tricyclic polyketides with antitumor activity which are produced by different streptomycete species. These members are glycosylated compounds with two oligosaccharide chains of variable sugar length. They interact with the DNA minor groove in high-GC-content regions in a nonintercalative way and with a requirement for magnesium ions. Mithramycin and chromomycins are the most representative members of the family, mithramycin being used as a… Expand
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References

SHOWING 1-10 OF 78 REFERENCES
The Biosynthesis of Aureolic Acid Group Antibiotics
Abstract Biosynthetic studies on mithramycin ( 1 , aureolic acid) using to a great extent modern genetic methods revealed several novel aspects of the biosynthesis of this class of antitumor agent.Expand
Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents.
TLDR
The aglycone moieties of mithramycin, chromomycin, and olivomycin are derived from a single polyketide backbone, which presumably involves decarboxylation and oxidative cleavage between C-18 and C-19, followed by additional oxidation, reduction, and methylation reactions. Expand
Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin.
TLDR
It is hypothesized that transcription of mtmOIV (encoding an oxygenase) was impaired in this strain, preventing oxidative breakage of the fourth ring of premithramycin B, a member of the clinically important aureolic acid group of antitumor drugs that interact with GC-rich regions of DNA nonintercalatively. Expand
Biosynthesis of the antitumor chromomycin A3 in Streptomyces griseus: analysis of the gene cluster and rational design of novel chromomycin analogs.
The biosynthetic gene cluster of the aureolic acid type antitumor drug chromomycin A3 from S. griseus subsp. griseus has been identified and characterized. It spans 43 kb and contains 36 genesExpand
Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin.
TLDR
The ElmGT glycosyltransferase from S. olivaceus Tü2353 can transfer different sugars into the aglycon 8-DMTC and can represent an important tool for combinatorial biosynthesis. Expand
Elucidation of the Glycosylation Sequence of Mithramycin Biosynthesis: Isolation of 3A‐Deolivosylpremithramycin B and Its Conversion to Premithramycin B by Glycosyltransferase MtmGII
TLDR
Results made it clear that both MtmGI and MtmGII take part in disaccharide formation, and it was unclear which GT catalyzes which exact step, since neither the GI nor the GII mutants accumulate exactly the same pattern of metabolites. Expand
Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mi
TLDR
Gen inactivation and analysis of the accumulated products revealed that both genes encode enzymes participating in the biosynthesis of the D-mycarose building block, revealing surprising substrate flexibility of post-PKS enzymes of the mithramycin biosynthetic pathway. Expand
Tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin A3 by Streptomyces griseus ssp. griseus
TLDR
The same single membrane‐bound enzyme, encoded by the cmmA gene, is responsible for both acetyl transfer reactions, which convert a relatively inactive compound into the bioactive chromomycin A3, one of the aureolic acid group family of antitumour drugs. Expand
MtmMII-mediated C-Methylation during Biosynthesis of the Antitumor Drug Mithramycin Is Essential for Biological Activity and DNA-Drug Interaction*
TLDR
The dinucleotide binding model fit well the isotherms recorded for both compounds, predicting that the C-7 methyl group was essential for high affinity binding to specific GC and CG sequences. Expand
Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp.
TLDR
The results thus elucidate the biosynthesis steps, products and the genes responsible for the reactions needed to build up an anthracyclinone. Expand
...
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