Hybridorubrins A-D: Azaphilone Heterodimers from Stromata of Hypoxylon fragiforme and Insights into the Biosynthetic Machinery for Azaphilone Diversification.
Hybridorubrins A-D: Azaphilone Heterodimers from Stromata of Hypoxylon fragiforme and Insights into the Biosynthetic Machinery for Azaphilone Diversification.
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DOI：
10.1002/chem.202003215
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发表时间：
2021-01-18
期刊：
影响因子：
--
通讯作者：
Surup F
中科院分区：
文献类型：
--
作者：
Becker K;Pfütze S;Kuhnert E;Cox RJ;Stadler M;Surup F
利用生物信息学方法研究了草莓形炭团菌（Hypoxylon fragiforme）子层提取物中氮杂菲酮类化合物的多样性，并将其与生物合成机制联系起来。共分离得到19个氮杂菲酮类化合物，通过核磁共振和质谱进行了表征，并利用Mosher酯分析和电子圆二色谱对其绝对立体构型进行了归属。除了新的fragirubrin F和G以及各种已知的mitorubrin衍生物之外，还阐明了四种前所未有的双氮杂菲酮，命名为杂交红蛋白A-D。只有由mitoruridine和fragiruridine部分组成的杂交红蛋白对金黄色葡萄球菌生物膜形成表现出强烈的抑制作用。对草莓形红球藻基因组的分析揭示了两个独立的生物合成基因簇（BGC）hfaza 1和hfaza 2的存在，这两个基因簇负责azaphilone的形成。 虽然hfaza 1 BGC可能编码主链的组装和脂肪酸部分的添加以产生（R）-构型系列的fragirubrin，但hfaza 2 BGC含有合成广泛分布的（S）-线粒体红蛋白所必需的基因。这项研究是两个远距离交叉作用真菌BGC合作产生两个家族的azaphilones和由此衍生的双azaphilones的第一个例子。 两个变成一个！杂交红蛋白A-D是前所未有的从子囊菌的脆形炭团菌（Hypoxylon fragiforme）的子座分离的双氮杂菲酮，由mitorubrin-和fragirubrin-型部分组成。正如基因组分析所揭示的那样，两个相距遥远的生物合成基因簇共同作用形成这些前体。与它们的结构单元相反，杂交红蛋白对金黄色葡萄球菌的生物膜形成表现出强的抑制活性。
The diversity of azaphilones in stromatal extracts of the fungus Hypoxylon fragiforme was investigated and linked to their biosynthetic machineries by using bioinformatics. Nineteen azaphilone‐type compounds were isolated and characterized by NMR spectroscopy and mass spectrometry, and their absolute stereoconfigurations were assigned by using Mosher ester analysis and electronic circular dichroism spectroscopy. Four unprecedented bis‐azaphilones, named hybridorubrins A–D, were elucidated, in addition to new fragirubrins F and G and various known mitorubrin derivatives. Only the hybridorubrins, which are composed of mitorubrin and fragirubrin moieties, exhibited strong inhibition of Staphylococcus aureus biofilm formation. Analysis of the genome of H. fragiforme revealed the presence of two separate biosynthetic gene clusters (BGCs) hfaza1 and hfaza2 responsible for azaphilone formation. While the hfaza1 BGC likely encodes the assembly of the backbone and addition of fatty acid moieties to yield the (R)‐configured series of fragirubrins, the hfaza2 BGC contains the necessary genes to synthesise the widely distributed (S)‐mitorubrins. This study is the first example of two distant cross‐acting fungal BGCs collaborating to produce two families of azaphilones and bis‐azaphilones derived therefrom. Two become one! Hybridorubrins A–D, unprecedented bis‐azaphilones isolated from the stromata of the ascomycete Hypoxylon fragiforme, are composed of mitorubrin‐ and fragirubrin‐type moieties. As revealed by genome analysis, two distantly located biosynthetic gene clusters work together to form these precursors. In contrast to their building blocks, the hybridorubrins exhibit strong inhibitory activity against biofilm formation of Staphylococcus aureus.
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影响因子：
5.1
作者：
Quang, DN;Hashimoto, T;Asakawa, Y
通讯作者：
Asakawa, Y
DOI：
10.3390/molecules22101663
发表时间：
2017-10-05
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
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通讯作者：
Gerothanassis IP
影响因子：
12.9
作者：
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通讯作者：
Narayan, Alison R. H.
影响因子：
14.8
作者：
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通讯作者：
Shao, Feng
影响因子：
5.5
作者：
Becker, Kevin;Wessel, Anna-Charleen;Stadler, Marc
通讯作者：
Stadler, Marc