Kohamaic acid A, a novel sesterterpenic acid, inhibits activities of DNA polymerases from deuterostomes

Abstract

We previously found and isolated a novel natural product, designated kohamaic acid A (KA-A), which inhibited the first cleavage of fertilized sea urchin eggs. In this paper, we report that this compound could selectively inhibit the activities of DNA polymerases (pol. α, β, γ, δ and ε) only from species in the deuterostome branch in the animal kingdom, like sea urchin, fish and mammals, but not from protostomes including insects (fruit fly, Drosophila melanogaster) and mollusks (octopus and oyster). Inhibition of deuterostome DNA polymerases was dose dependent. IC 50 values for DNA polymerases of mammals and fish occurred at approximately 5.8–14.9 μM and those of sea urchin at 6.1–30.3 μM. In the sea urchin DNA polymerases, the activities of the replicative DNA polymerases such as α, δ and ε were more strongly inhibited than that of the repair-related pol. β. KA-A is an inhibitor of replicative DNA polymerases from the deuterostome species, and subsequently, the inhibition of the first cleavage of fertilized sea urchin eggs might occur as a result of the suppression of DNA replication.