Tang Jia, Matsuda Yudai
Department of Chemistry, City University of Hong Kong Tat Chee Avenue Kowloon Hong Kong SAR China
Chem Sci. 2022 Aug 17;13(35):10361-10369. doi: 10.1039/d2sc02994d. eCollection 2022 Sep 14.
The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized the cyclization of (6,10')-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase-InsB2-also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways.
芳香族聚酮化合物3,5-二甲基苔色酸（DMOA）是许多真菌杂萜类化合物的前体。大部分源自DMOA的杂萜类化合物是通过(6,10')-环氧法呢基-DMOA甲酯（1）的环化生物合成的。理论上，虽然1可以环化生成许多产物，但仅报道了三种环化模式。在此，我们在CBS 107.25中发现了一个杂萜类生物合成基因簇，其编码1的生物合成酶以及一种与1的其他已表征环化酶在系统发育上关系较远的萜烯环化酶。有趣的是，萜烯环化酶InsA7将1折叠成预船椅构象，生成一种在C3处具有轴向羟基的新杂萜类化合物。该菌株还含有另一个编码1的另一种环化酶的基因簇。第二种萜烯环化酶InsB2也合成1的一种新环化产物，从而导致该真菌生物合成途径的分歧。最后，我们对这两个基因簇编码的修饰酶进行了表征，总共获得了17种新的杂萜类化合物，并成功提出了通向两条途径明显终产物的生物合成路线。
