Ambruticins: An inspiration to develop novel biocatalysts and antifungal agents

生物合成研究为遗传学和酶学提供了引人入胜的见解，为清洁和有效地合成生物活性天然产物带来了操纵途径的前景。我们的目标是利用生物合成的力量，不仅合理地操纵途径本身，提供新的生物活性化合物和生物催化剂，而且作为一种灵感，开发新的高效合成策略，以建立一个在作物科学和药物化学中具有潜在价值的富含SP3的支架文库。AmBruticins是由孢子囊纤维产生的多酮类天然产物，它们具有强大的抗真菌活性。它们是复杂的，具有许多有趣的结构特征，包括九个不对称中心，一个甲基环丙基和两个氧杂环。我们将研究生物合成途径的关键步骤，长期目标是提供广泛实用的生物催化剂。此外，将开发首次完全合成关键的拟议中间体AmBruticin J，理想情况下将使用一种通用的仿生策略，该策略将适用于提供天然产品的类似物作为潜在的新抗真菌药物。

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.