Cetoniacytone A

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Cetoniacytone A
Names
IUPAC name
N-[(1R,2S,6R)-2-hydroxy-6-(hydroxymethyl)-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]acetamide
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
  • InChI=1S/C9H11NO5/c1-4(12)10-5-2-6(13)9(3-11)8(15-9)7(5)14/h2,7-8,11,14H,3H2,1H3,(H,10,12)/t7-,8+,9-/m0/s1
    Key: JYYJQJKNUQRQSW-YIZRAAEISA-N
  • CC(=O)NC1=CC(=O)[C@]2([C@@H]([C@H]1O)O2)CO
Properties
C9H11NO5
Molar mass 213.189 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Cetoniacytone A is a secondary metabolite classified in the family of C7N aminocyclitols which include other natural products such as validamycin A, acarbose, and epoxyquinomicin.[1] Cetoniacytone A was first identified from a culture of Actinomyces sp. (strain Lu 9419), an endosymbiotic Gram-positive bacillus found in the intestines of a rose chafer (Cetonia aureata).[2] Preliminary feeding studies with [U-13C3]glycerol identified the core moiety, cetoniacytone, to be derived via the pentose phosphate pathway. Although agar plate diffusion assay studies of cetoniacytone A showed no antimicrobial activity against Gram-positive and Gram-negative bacteria, cetoniacytone A has demonstrated a significant growth inhibitory effect against human cancer cell lines including hepatocellular carcinoma (HEP G2) and breast adenocarcinoma (MCF 7).[2][3]

Biosynthesis

Feeding experiments conducted by Zeeck and co-workers established the synthesis of Cetoniacytone A to proceed via the pentose phosphate pathway with sedoheptulose-7- phosphate as the key intermediate.[2] Sedoheptulose-7- phosphate first undergoes a cyclization catalyzed by 2-epi-5-epi-valiolone synthase (CetA) yielding 2-epi-5-epi-valiolone. Following the cyclization, 2-epi-5-epi-valiolone epimerase (CetB) results in an inversion of the stereochemistry of the alcohol alpha to the ketone forming 5-epi-valiolone. Next, CetL, a type of oxidoreductase, results in the oxidation of the C-4 hydroxyl group to give 2-keto-5-epi-valiolone followed by a transamination catalyzed by aminotransferases CetM to give 2-amino-5-epi-valiolone. The sequential reactions depicted in the dashed box represent putative pathways that involve oxidoreductase, dehydrogenase, and hypothetical proteins related to the cupin superfamily to yield cetoniacytone B. Lastly, cetoniacytone B is acetylated via an arylamine N-acetyltransferase (CetD) to yield cetoniacytone A.[3]

Figure 1. Biosynthesis of Cetoniacytone A from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419.[2]

References

  1. ^ Mahmud, Taifo (2003). "The C7N aminocyclitol family of natural products". Natural Product Reports. 20 (2): 137–166. doi:10.1039/B205561A. PMID 12636088.
  2. ^ a b c d Schlorke O, Krastel P, Muller I, Uson I, Dettner K, and Zeeck A (2002). "Structure and Biosynthesis of Cetoniacytone A, a Cytotoxic Aminocarba Sugar Produced by an Endosymbiontic Actinomyces". Journal of Antibiotics. 55 (7): 635–642. doi:10.7164/antibiotics.55.635. PMID 12243453.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ a b Wu X, Flatt M, Xu H, and Mahmud T (2009). "Biosynthetic Gene Cluster of Cetoniacytone A, an Unusual Aminocyclitol from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419". ChemBioChem. 10 (2): 304–314. doi:10.1002/cbic.200800527. PMC 3136446. PMID 19101977.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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