The type II polyketide A-74528 inhibits 2',5'-oligoadenylate phosphodiesterase, a key regulatory enzyme in the a-interferon pathway.  In addition to its novel bioactivity, at 30 carbons it is tied for the largest type II polyketide natural product known.  We have previously sequenced and heterologously expressed the gene cluster responsible for the production of A-74528, which unexpectedly also produces the structurally unrelated polyketide fredericamycin A.  Here we present our efforts toward understanding and engineering A-74528 biosynthesis through reconstruction in a heterologous host.

Probing the biosynthesis of the type II polyketide A-74528 through heterologous pathway reconstruction

243rd National Meeting (2012)

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