Ambruticins: An inspiration to develop novel biocatalysts and antifungal agents

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Biosynthetic studies are providing fascinating insights into genetics and enzymology leading to the prospect of manipulating pathways for the clean and efficient synthesis of bioactive natural products Our goal is to harness the power of biosynthesis not only for the rational manipulation of the pathways themselves to provide new bioactive compounds and biocatalysts, but also as an inspiration to develop new and efficient synthetic strategies to a library of sp3-rich scaffolds of potential value in both crop science and medicinal chemistry.Ambruticins are polyketide-derived natural products produced by Sporangium cellulosum and they exhibit potent antifungal activity. They are complex with many interesting structural features including nine asymmetric centres, a methyl cyclopropyl group and two oxygen heterocycles. We will investigate key steps of the biosynthetic pathway with the longer-term goal of providing biocatalysts of widespread utility. Furthermore, the first total synthesis of a key proposed intermediate, ambruticin J, will be developed, ideally using a versatile biomimetic strategy which will be adapted to provide analogues of the natural product as potential new antifungal agents.