Abstract

Meroterpenoids are hybrid compounds that are partially derived from terpenoids. This group of natural products displays large structural diversity, and many members exhibit beneficial biological activities. This mini-review highlights recent advances in the engineered biosynthesis of meroterpenoid compounds with C15 and C20 terpenoid moieties, with the reconstruction of fungal meroterpenoid biosynthetic pathways in heterologous expression hosts and the mutagenesis of key enzymes, including terpene cyclases and α-ketoglutarate (αKG)-dependent dioxygenases, that contribute to the structural diversity. Notable progress in genome sequencing has led to the discovery of many novel genes encoding these enzymes, while continued efforts in X-ray crystallographic analyses of these enzymes and the invention of AlphaFold2 have facilitated access to their structures. Structure-based mutagenesis combined with applications of unnatural substrates has further diversified the catalytic repertoire of these enzymes. The information in this review provides useful knowledge for the design of biosynthetic machineries to produce a variety of bioactive meroterpenoids.

Beilstein J. Org. Chem. 2024, 20, 578–588. doi:10.3762/bjoc.20.50

摘要

类萜是部分源自萜类化合物的混合化合物。这组天然产物表现出巨大的结构多样性，许多成员表现出有益的生物活性。这篇小综述重点介绍了具有 C15 和 C20 萜类部分的类萜化合物工程生物合成的最新进展，以及异源表达宿主中真菌类萜生物合成途径的重建以及包括萜烯环化酶和 α-酮戊二酸 (αKG) 在内的关键酶的诱变-依赖性双加氧酶，有助于结构多样性。基因组测序的显着进展导致发现了许多编码这些酶的新基因，而对这些酶的 X 射线晶体学分析的持续努力以及 AlphaFold2 的发明促进了对其结构的了解。基于结构的诱变与非天然底物的应用相结合，进一步丰富了这些酶的催化能力。本综述中的信息为设计生产各种生物活性美萜类化合物的生物合成机械提供了有用的知识。

贝尔斯坦 J. 组织。化学。 2024, 20, 578–588。doi:10.3762/bjoc.20.50