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., an endosymbiotic Gram-positive bacillus found in the intestines of a rose chafer. Preliminary feeding studies with 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 and breast adenocarcinoma.
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 yielding 2-epi-5-epi-valiolone. Following the cyclization, 2-epi-5-epi-valiolone epimerase 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 to yield cetoniacytone A.