Cetoniacytone A

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. 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). 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).

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. 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.