The azinomycins are of interest due to their anti-tumor capabilities, which results from their ability to crosslink DNA. This directly implies use as an anti-cancer agent. As the naphthoate moiety is one structural feature of the natural product that imparts stability in its ability to bind DNA, we turned our attention to the mechanism by which this ring-based moiety is formed. Moreover, as complex ring structures are invaluable in synthesis (primarily pharmaceuticals), a better understanding of the enzymatic formation of these rings could prove to be extremely useful. In previous work, it was suspected that the naphthoate moiety was formed by a type of polyketide synthase (PKS), AziB. Earlier studies, however, showed that this was not the case in regard to AziB alone. Another protein, AziG (thioesterase domain), appeared to be responsible for completion of the naphthoate moiety. To further evaluate these findings, here we invoke point mutations within the proposed active site of AziG. We hypothesize that, if these loci contribute to naphthoate formation, these mutations will result in the inability of AziB and AziG to synthesize the naphthoate moiety and we may obtain a better understanding of the overall mechanism.

Role of the thioesterase domain, AziG, in the formation of the naphthoate moiety in azinomycins

247th National Meeting (2014)

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