Welcome to CDC stacks | Identification and Characterization of the Echinocandin B Biosynthetic Gene Cluster from Emericella rugulosa NRRL 11440 - 33455 | CDC Public Access
Stacks Logo
Advanced Search
Select up to three search categories and corresponding keywords using the fields to the right. Refer to the Help section for more detailed instructions.
 
 
Help
Clear All Simple Search
Advanced Search
Identification and Characterization of the Echinocandin B Biosynthetic Gene Cluster from Emericella rugulosa NRRL 11440
Filetype[PDF-1.60 MB]


Details:
  • Pubmed ID:
    22998630
  • Pubmed Central ID:
    PMC3482383
  • Description:
    Echinocandins are a family of fungal lipidated cyclic hexapeptide natural products. Due to their effectiveness as antifungal agents, three semisynthetic derivatives have been developed and approved for treatment of human invasive candidiasis. All six of the amino acid residues are hydroxylated, including 4R,5R-dihydroxy-L-ornithine, 4R-hydroxyl-L-proline, 3S,4S-dihydroxy-L-homotyrosine, and 3S-hydroxyl-4S-methyl-L-proline. We report here the biosynthetic gene cluster of echinocandin B 1 from Emericella rugulosa NRRL 11440 containing genes encoding for a six-module nonribosomal peptide synthetase EcdA, an acyl-AMP ligase EcdI, and oxygenases EcdG, EcdH, and EcdK. We showed EcdI activates linoleate as linoleyl-AMP and installs it on the first thiolation domain of EcdA. We have also established through ATP-PP(i) exchange assay that EcdA loads L-ornithine in the first module. A separate hty gene cluster encodes four enzymes for de novo generation of L-homotyrosine from acetyl-CoA and 4-hydroxyphenyl-pyruvate is found from the sequenced genome. Deletions in the ecdA, and htyA genes validate their essential roles in echinocandin B production. Five predicted iron-centered oxygenase genes, ecdG, ecdH, ecdK, htyE, and htyF, in the two separate ecd and hty clusters are likely to be the tailoring oxygenases for maturation of the nascent NRPS lipohexapeptidolactam product.

  • Document Type:
  • Collection(s):
  • Funding:
    1DP1GM106413/DP/NCCDPHP CDC HHS/United States
    1R01GM092217/GM/NIGMS NIH HHS/United States
    1R01GM49338/GM/NIGMS NIH HHS/United States
    DP1 GM106413/GM/NIGMS NIH HHS/United States
    GM08496/GM/NIGMS NIH HHS/United States
    R01 GM092217/GM/NIGMS NIH HHS/United States
No Related Documents.
You May Also Like: