Ribosomal biosynthesis of the cyclic peptide toxins of Amanita mushrooms.

Ribosomal biosynthesis of the cyclic peptide toxins of Amanita mushrooms.
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DOI:
10.1002/bip.21416
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发表时间:
2010
期刊:
影响因子:
2.9
通讯作者:
Luo, Hong
Luo, Hong
中科院分区:
生物学4区
文献类型:
--
作者:
Walton, Jonathan D.;Hallen-Adams, Heather E.;Luo, Hong

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鹅膏菌属的某些种类的蘑菇具有极强的毒性,经常对包括人类和狗在内的哺乳动物致命。它们的极端毒性是由于鹅膏毒素如α-和β-鹅膏蕈碱。鹅膏蕈类还生物合成一组化学相关的毒素,鬼笔毒素,如鬼笔环肽。鹅膏毒素和鬼笔毒素(统称鹅膏毒素)分别是双环八肽和七肽。两者都含有一个不寻常的Trp-Cys交叉桥,称为色氨酸。我们已经表明,在鹅膏菌bisporigera,鹅膏毒素和phallotoxins的核糖体上,而不是由非核糖体肽合成酶的前蛋白合成。前蛋白的长度为34-35个氨基酸,并且没有预测的信号肽。α-鹅膏毒肽(AMA 1)和鬼笔毒肽(PHA 1)的基因是相关基因大家族的成员,其特征在于侧翼高变“毒素”区域的高度保守氨基酸序列。毒素区域的侧翼是不变的脯氨酸(Pro)残基。从产鬼笔环肽的蘑菇中分离纯化了一种切割鬼笔环肽前蛋白的酶。该酶是脯氨酰寡肽酶(POP)亚家族中的丝氨酸蛋白酶。相同的酶切割两个Pro残基以释放线性七肽或八肽。
Some species of mushrooms in the genus Amanita are extremely poisonous and frequently fatal to mammals including humans and dogs. Their extreme toxicity is due to amatoxins such as α- and β-amanitin. Amanita mushrooms also biosynthesize a chemically related group of toxins, the phallotoxins, such as phalloidin. The amatoxins and phallotoxins (collectively known as the Amanita toxins) are bicyclic octa- and heptapeptides, respectively. Both contain an unusual Trp-Cys cross-bridge known as tryptathionine. We have shown that, in Amanita bisporigera, the amatoxins and phallotoxins are synthesized as proproteins on ribosomes and not by nonribosomal peptide synthetases. The proproteins are 34–35 amino acids in length and have no predicted signal peptides. The genes for α-amanitin (AMA1) and phallacidin (PHA1) are members of a large family of related genes, characterized by highly conserved amino acid sequences flanking a hypervariable “toxin” region. The toxin regions are flanked by invariant proline (Pro) residues. An enzyme that could cleave the proprotein of phalloidin was purified from the phalloidin-producing lawn mushroom Conocybe apala. The enzyme is a serine protease in the prolyl oligopeptidase (POP) subfamily. The same enzyme cuts at both Pro residues to release the linear hepta- or octapeptide.
DOI: 10.1074/jbc.m109.006460
发表时间: 2009-07-03
影响因子: 4.8
作者:
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发表时间: 2009-04
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发表时间: 2003-11-25
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发表时间: 2008-06-01
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