Controlling a structural branch point in ergot alkaloid biosynthesis.

Controlling a structural branch point in ergot alkaloid biosynthesis.
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DOI:
10.1021/ja105785p
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发表时间:
2010-09-22
影响因子:
15
通讯作者:
O'Connor, Sarah E.
O'Connor, Sarah E.
中科院分区:
化学1区
文献类型:
--
作者:
Cheng, Johnathan Z.;Coyle, Christine M.;Panaccione, Daniel G.;O'Connor, Sarah E.

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麦角类生物碱是一类真菌来源的吲哚类生物碱天然产物,具有很强的药理活性。生物合成中间体裸花黄素-I醛1代表麦角生物合成中的分支点。麦角生物碱festuclavine 2和农麦角碱3衍生自源自共同的生物合成前体裸麦角碱-I醛1的交替酶促途径。在这里,我们表明,而老黄酶同系物EasA从麦角生物合成基因簇的烟曲霉作用于裸麦角碱-I醛1产生festuclavine 2,EasA从Neotyphodium lolii,相比之下,产生农棒麦角碱3。突变分析表明,控制麦角生物碱生物合成的这个关键分支点的活性转换的机制原理。
The ergot alkaloids are a diverse class of fungal-derived indole alkaloid natural products with potent pharmacological activities. The biosynthetic intermediate chanoclavine-I aldehyde 1 represents a branch point in ergot biosynthesis. Ergot alkaloids festuclavine 2 and agroclavine 3 derive from alternate enzymatic pathways originating from the common biosynthetic precursor chanoclavine-I aldehyde 1. Here we show that while the Old Yellow Enzyme homolog EasA from the ergot biosynthetic gene cluster of Aspergillus fumigatus acts on chanoclavine-I aldehyde 1 to yield festuclavine 2, EasA from Neotyphodium lolii, in contrast, produces agroclavine 3. Mutational analysis suggests a mechanistic rationale for the switch in activity that controls this critical branch point of ergot alkaloid biosynthesis.
DOI: 10.1074/jbc.273.49.32763
发表时间: 1998-12-04
影响因子: 4.8
作者:
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发表时间: 2010-06-01
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