Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745, Jena, Germany.
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202116142. doi: 10.1002/anie.202116142. Epub 2022 Apr 12.
(Pre-)anthraquinones are widely distributed natural compounds and occur in plants, fungi, microorganisms, and animals, with atrochrysone (1) as the key biosynthetic precursor. Chemical analyses established mushrooms of the genus Cortinarius-the webcaps-as producers of atrochrysone-derived octaketide pigments. However, more recent genomic data did not provide any evidence for known atrochrysone carboxylic acid (4) synthases nor any other polyketide synthase (PKS) producing oligocyclic metabolites. Here, we describe an unprecedented class of non-reducing (NR-)PKS. In vitro assays with recombinant enzyme in combination with in vivo product formation in the heterologous host Aspergillus niger established CoPKS1 and CoPKS4 of C. odorifer as members of a new class of atrochrysone carboxylic acid synthases. CoPKS4 catalyzed both hepta- and octaketide synthesis and yielded 6-hydroxymusizin (6), along with 4. These first mushroom PKSs for oligocyclic products illustrate how the biosynthesis of bioactive natural metabolites evolved independently in various groups of life.
（前）蒽醌类化合物广泛分布于自然界，存在于植物、真菌、微生物和动物中，其中atrochrysone（1）是关键的生物合成前体。化学分析确定了网孢牛肝菌属（Cortinarius）的蘑菇，即网孢蘑菇，是atrochrysone 衍生的八酮色素的生产者。然而，最近的基因组数据并未提供任何已知的atrochrysone 羧酸（4）合成酶或任何其他产生寡环代谢物的聚酮合酶（PKS）的证据。在这里，我们描述了一类前所未有的非还原（NR-）PKS。用重组酶进行体外测定，并在异源宿主黑曲霉（Aspergillus niger）中进行体内产物形成，证实了 C. odorifer 的 CoPKS1 和 CoPKS4 是atrochrysone 羧酸合成酶的一个新类别。CoPKS4 催化七酮和八酮的合成，并产生 6-羟基麦角甾醇（6），以及 4。这些用于寡环产物的第一个蘑菇 PKS 说明了生物活性天然代谢物的生物合成如何在生命的各个群体中独立进化。
