The azinomycins, natural products produced by the bacteria <i>Streptomyces sahachiroi</i>, have exhibited promise as anti-cancer agents. Herein, studies concerning the biosynthesis and potential utility of these important compounds will be described. First, to continue previous investigation of the biosynthetic pathway to the azinomycin epoxide moiety crucial to azinomycin’s activity, the understood precursor to this epoxide  was partially synthesized. To confirm the hypothesized biosynthetic pathway, further studies will complete the synthesis of this precursor for use in a biological assay with AziA3, an enzyme associated with azinomycin’s epoxide formation. It is anticipated that the acquisition of a deeper understanding of the biosynthetic pathway of the azinomycins may lead to the development of a stronger vision for the development of anti-cancer agents that can selectively target cancer cells. Second, to demonstrate feasibility of potential methodology for application of azinomycin, survivin-thiaminase constructs were assembled as a proof of principle experiment. The survivin gene is over expressed in a variety of cancers and acts by inhibiting cell apoptosis. We aimed to link the survivin gene promoter to thiaminase, an enzyme that degrades thiamin (vitamin B1), with the goal of over-expressing thiaminase. The over-expression of thiaminase leads to cell death via the degeneration of vitamin B1. This method leaves healthy cells untouched as normal cells do no express survivin. Thus, linkage of survivin to thiaminase presents a possible method for the selective killing of cancer cells analogous to envisioned application of azinomycin.<br/>

Biosynthetic study of the formation of the azinomycin epoxide moiety

253rd National Meeting (2017)

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