Abstract

Fungal meroterpenoids are diverse structurally intriguing molecules with various biological properties. One large group within this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10′R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids.

Beilstein J. Org. Chem. 2024, 20, 638–644. doi:10.3762/bjoc.20.56

摘要

真菌类萜是结构多样、具有各种生物学特性的有趣分子。这一类化合物中的一大类衍生自芳香族前体 3,5-二甲基邻苯二甲酸 (DMOA)。在这项研究中，我们在米曲霉中构建了工程代谢途径，以扩大类萜的分子多样性。我们使用 5-甲基orellinic 酸 (5-MOA) 合酶 FncE 和另外三种生物合成酶来形成 (6 R ,10' R )-环氧法尼基-5-MOA 甲酯，其作为四种酶的非天然底物来自 DMOA 衍生的类萜途径的萜烯环化酶。结果，我们成功生成了六种非天然的 5-MOA 衍生的类萜物种，证明了我们的方法在生成类萜结构类似物方面的有效性。

贝尔斯坦 J. 组织。化学。 2024, 20, 638–644。doi:10.3762/bjoc.20.56