近日，中国农业大学Daowan Lai及其小组的研究发现，Palmarumycin 螺二萘（SBNs）生物合成的阐明揭示了一组以前未被识别的氧化酶和还原酶。相关论文于2024年4月6日发表在《德国应用化学》杂志上。

在这项研究中，通过基因破坏、异源基因表达和底物摄食实验，研究小组阐明了Palmarumycin的生物合成途径。Palmarumycin生物合成基因团簇与聚酮合成酶基因团簇距离较远，包含2个细胞色素P450 (PalA和PalB)和1个短链脱氢酶/还原酶(PalC)编码基因作为关键结构基因。PalA是一种非常见、多功能的P450，它催化1,8-二羟基萘的氧化二聚化反应，生成螺酮键和2,3-环氧基。

关键中间体的化学合成和体外生化实验证明，氧化二聚化反应是通过联萘醚进行的。PalB安装广泛存在于 螺二萘中的C-5羟基。PalC催化1-酮还原、逆1-脱氢和2,3-环氧化物还原。此外，一种由palD编码的FAD依赖性氧化还原酶位于细胞外，起1-脱氢酶的作用。这些结果为生物合成palmarumycin螺二萘提供了第一个遗传和生化证据。

据介绍， 螺二萘是一类高度氧化的真菌双萘，含有独特的螺酮桥，具有多种生物活性。在已报道的SBNs中，palmarumycin是主要类型，在结构上是其他类型SBNs的前体。然而，SBNs的生物合成尚不清楚。

附：英文原文

Title: Elucidation of Palmarumycin Spirobisnaphthalene Biosynthesis Reveals a Set of Previously Unrecognized Oxidases and Reductases

Author: Siji Zhao, Zhen Shen, Ziqi Zhai, Ruya Yin, Dan Xu, Mingan Wang, Qi Wang, You-Liang Peng, Ligang Zhou, Daowan Lai

Issue&Volume: 2024-04-06

Abstract: Spirobisnaphthalenes (SBNs) are a class of highly oxygenated, fungal bisnaphthalenes containing an unique spiroketal bridge, that displayed diverse bioactivities. Among the reported SBNs, palmarumycins are the major type, which are precursors for the other type of SBNs structurally. However, the biosynthesis of SBNs is unclear. In this study, we elucidated the biosynthesis of palmarumycins, using gene disruption, heterologous expression, and substrate feeding experiments. The biosynthetic gene cluster for palmarumycins was identified to be distant from the polyketide synthase gene cluster, and included two cytochrome P450s (PalA and PalB), and one short chain dehydrogenase/reductase (PalC) encoding genes as key structural genes. PalA is an unusual, multifunctional P450 that catalyzes the oxidative dimerization of 1,8-dihydroxynaphthalene to generate the spiroketal linkage and 2,3-epoxy group. Chemical synthesis of key intermediate and in vitro biochemical assays proved that the oxidative dimerization proceeded via a binaphthyl ether. PalB installs the C-5 hydroxyl group, widely found in SBNs. PalC catalyzes 1-keto reduction, the reverse 1-dehydrogenation, and 2,3-epoxide reduction. Moreover, an FAD-dependent oxidoreductase, encoded by palD, which locates outside the cluster, functions as 1-dehydrogenase. These results provided the first genetic and biochemical evidence for the biosynthesis of palmarumycin SBNs.

DOI: 10.1002/anie.202401979

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202401979