Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger

Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger
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DOI:
10.1016/j.chembiol.2014.01.013
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发表时间:
2014-04-24
影响因子:
--
通讯作者:
Mortensen, Uffe H.
Mortensen, Uffe H.
中科院分区:
生物1区
文献类型:
--
作者:
Holm, Dorte K.;Petersen, Lene M.;Mortensen, Uffe H.

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丝状真菌的次级代谢产物是生物活性分子的丰富来源。我们推测了尼日尔曲霉中抗生素黄怒酮D的遗传和生物合成途径。我们的分析表明,yanuthone D是一个merotenoid衍生自聚酮6-甲基水杨酸(6-MSA)。Yanuthone D的形成依赖于由10个基因组成的簇,包括yanA和yanl,它们分别编码6-MSA聚酮合酶和先前未描述的O-甲羟戊酸转移酶。此外,在该途径中发现了几个分支点,揭示了五个yanuthone(F,G,H,I和J)。此外,我们已经确定了另一种化合物(yanuthone X-1),它定义了一类yanuthone,依赖于几个酶活性编码的基因在yan集群,但不是来自6-MSA。
Secondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanl, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X-1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA.