Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in Aspergillus terreus revealed by genome-based deletion analysis.

Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in Aspergillus terreus revealed by genome-based deletion analysis.
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DOI:
10.1021/ja3123653
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发表时间:
2013-05-15
影响因子:
15
通讯作者:
Wang, Clay C. C.
Wang, Clay C. C.
中科院分区:
化学1区
文献类型:
--
作者:
Guo, Chun-Jun;Yeh, Hsu-Hua;Chiang, Yi-Ming;Sanchez, James F.;Chang, Shu-Ling;Bruno, Kenneth S.;Wang, Clay C. C.

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表聚硫代二氧代哌嗪(epipolithiodioxopiperazines,ETP)是一类由二酮哌嗪衍生的真菌次生代谢产物。乙酰羊毛素属于ETP的一个结构亚组,其特征在于存在七元4,5-二氢氧杂环。确定参与acetylaranotin生物合成的基因应该提供一种方法来增加这些化合物的生产,并促进第二代分子的工程。丝状真菌Aspergillus terreus产生乙酰基羊毛素和相关的天然产物。使用有针对性的基因缺失,我们已经确定了一个集群的9个基因,包括一个非核糖体肽合成酶基因,ataP,这是所需的acetylaranotin的生物合成。对野生型和突变株的化学分析使我们能够从乙酰羊毛素生物合成途径中分离出17种天然产物。在这项研究中发现的9种化合物是以前没有报道的天然产物。我们的数据使我们能够提出一个生物合成途径乙酰拉诺廷和相关的天然产物。
Epipolythiodioxopiperazines (ETPs) are a class of fungal secondary metabolites derived from diketopiperazines. Acetylaranotin belongs to one structural subgroup of ETPs characterized by the presence of a seven-membered 4,5-dihydrooxepine ring. Defining the genes involved in acetylaranotin biosynthesis should provide a means to increase production of these compounds and facilitate the engineering of second-generation molecules. The filamentous fungus Aspergillus terreus produces acetylaranotin and related natural products. Using targeted gene deletions, we have identified a cluster of nine genes including one nonribosomal peptide synthetase gene, ataP, which is required for acetylaranotin biosynthesis. Chemical analysis of the wild type and mutant strains enabled us to isolate seventeen natural products from the acetylaranotin biosynthesis pathway. Nine of the compounds identified in this study are previously not reported natural products. Our data allow us to propose a biosynthetic pathway for acetylaranotin and related natural products.
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