Heterologous biosynthesis of nodulisporic acid

Abstract

Nodulisporic acids (NAs) comprise a group of indole diterpenes known for their potent insecticidal activities; however, biosynthesis of NAs by its natural producer, Hypoxylon pulicicidum (Nodulisporium sp.) is exceptionally difficult to achieve. The identification of genes responsible for NA production could enable biosynthetic pathway optimization to provide access to NAs for commercial applications. Obtaining useful quantities of NAs using published fermentations methods is challenging, making gene knockout studies an undesirable method to confirm gene function. Alternatively, heterologous gene expression of H. pulicicidum genes in a more robust host species like Penicillium paxilli provides a way to rapidly identify the function of genes that play a role in NA biosynthesis. In this work, we identified the function of four secondary-metabolic genes necessary for the biosynthesis of nodulisporic acid F (NAF) and reconstituted these genes in the genome of P. paxilli to enable heterologous production of NAF in this fungus.

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